Gudrun Høiseth

• Havig, Stine Marie; Høiseth, Gudrun; Thaulow, Cecilie Hasselø; Green, Henrik; Skurtveit, Svetlana Ondrasova & Edvardsen, Hilde Marie Erøy (2026). Prescription status and drug concentrations in methadone intoxications versus non-intoxications: A registry-linked study of autopsy cases. Forensic Science International. ISSN 0379-0738. 388. doi: 10.1016/j.forsciint.2026.113084. Fulltekst i vitenarkiv Vis sammendrag

  Aims Limited information exists on characteristics associated with methadone intoxication deaths. We therefore aimed to describe and explore differences in demographics, methadone prescription status, and drug concentrations in deaths with methadone, comparing intoxications with non-intoxications. Methods 1092 forensic autopsy cases with methadone detected in blood analyzed at Oslo University Hospital (2004–2021) were linked to the Norwegian Cause of Death Registry and the Norwegian Prescribed Drug Registry. Cases were grouped as methadone intoxication (n = 638), other intoxication (n = 252), and non-intoxication (n = 202). Non-parametric tests (Chi-squared, Mann–Whitney U) and logistic regression analyses were used to compare demographic variables, prescription status, and drug concentrations (opioids, benzodiazepines, stimulants, ethanol) between intoxications and non-intoxications. Results Methadone prescription was less common in methadone intoxications and other intoxications than in non-intoxications (28.8% and 27.4% vs. 59.9%, respectively; P < 0.001 for both). Methadone intoxications were associated with younger age (adjusted odds ratio [aOR] 0.96; 95% confidence interval [CI] 0.95–0.98) and no recent methadone prescription (aOR 3.01; 95% CI 2.04–4.44) compared with non-intoxications. Adjusted analyses revealed no significant difference in methadone concentration between these groups. However, among cases with prescription, methadone intoxications were associated with higher methadone concentration (aOR 1.20; 95% CI 1.09–1.32). Intoxications also involved more psychoactive drugs and more frequent detections of benzodiazepines and stimulants. Conclusion Our results support that the determination of fatal methadone intoxications cannot be based solely on interpretation of postmortem methadone concentrations in blood but is dependent on information about prescription status and degree of tolerance.

• Bramness, Jørgen Gustav; Mørland, Jørg Gustav; Lid, Torgeir Gilje; Høye, Anne & Høiseth, Gudrun (2026). The impact of drinking patterns on the relationship between alcohol use and levels of serum high-density lipoprotein cholesterol (HDL-C). Alcohol. ISSN 0741-8329. 135, s. 70–76. doi: 10.1016/j.alcohol.2026.07.003. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Olsen, Thomas; Mørland, Jørg Gustav; Hjelmeland, Knut Johan & Strand, Maren (2026). Associations between blood ethanol concentration, clinical impairment test results, and traffic accident involvement among apprehended drivers. Traffic Injury Prevention. ISSN 1538-9588. doi: 10.1080/15389588.2026.2688460.
• Midtlyng, Lena; Høiseth, Gudrun; Rahho, Rafika & Thaulow, Cecilie Hasselø (2025). Exploring the “poppy seed defense” in oral fluid: detection of opioids following poppy seed consumption. Journal of Analytical Toxicology. ISSN 0146-4760. doi: 10.1093/jat/bkaf088. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The “poppy seed defense”—a claim that a positive opioid test result is due to ingestion of poppy seeds—is occasionally encountered in forensic toxicology. The matter has been thoroughly investigated in urine but is less researched in oral fluid. We therefore aimed to perform an experimental study to explore whether consumption of commercially available poppy seeds would lead to detection of opioids in oral fluid. Additionally, we aimed to relate our findings to routine cases. Ten volunteers consumed either five crispbreads containing a small amount of poppy seeds, or 30 g of raw poppy seeds with a low opioid content (3.0 mg/kg morphine and 0.9 mg/kg codeine). Oral fluid samples were collected 0.5 and 2 hours after consumption. Additionally, a urine sample was collected 2 hours after consumption. Following ingestion of raw seeds, morphine was detected (estimated neat oral fluid concentrations 1.4–5.6 ng/mL) in all oral fluid samples 0.5 hours after consumption and in one (2.4 ng/mL) of five oral fluid samples after 2 hours. Codeine was detected (0.8–1.1 ng/mL) in three of five oral fluid samples 0.5 hours after consumption, but in none after 2 hours. Following ingestion of crispbreads, morphine or codeine was not detected in oral fluid, but opioids/-glucuronides were detected in three of five urine samples. When comparing our results with routine cases, we found that 14% of routine cases had morphine concentrations in oral fluid samples lower or similar to those seen after ingestion of raw seeds in our experimental study. In conclusion, we found that consumption of raw seeds led to detection of opioids in oral fluid, but the detection window appeared to be short. Comparison with routine cases indicated that the poppy seed defense may be a challenge when interpreting oral fluid results, particularly when low cut-off levels are applied.

• Fosen, Jan Toralf; Bleka, Øyvind; Hjelmeland, Knut Johan; Kristoffersen, Lena & Høiseth, Gudrun (2025). Elimination of EtG and EtS between two consecutive blood samples in apprehended drivers. Forensic Science International. ISSN 0379-0738. 378. doi: 10.1016/j.forsciint.2025.112700. Fulltekst i vitenarkiv Vis sammendrag

  Aim Ethyl glucuronide (EtG) and ethyl sulphate (EtS) are non-oxidative metabolites of ethanol, valuable as biomarkers of alcohol consumption in forensic and clinical contexts. This study aims to calculate the elimination half-lives (t₁/₂) of EtG and EtS in apprehended drivers based on two consecutive blood samples, enhancing the reliability of forensic alcohol consumption assessments. Methods Data was extracted from a database including apprehended drivers in Norway from 2019 to 2024. The study included suspected drunk drivers in which ethanol, EtG and EtS were detected in two consecutive blood samples, drawn at least 20 min apart. In cases where the blood alcohol concentration (BAC) was at or below 0.20 g/kg, in at least one sample, the t₁/₂ was estimated using both empirical and Bayesian statistical methods. Results In 670 cases, ethanol, EtG and EtS were detected in two consecutive samples. In 20 of these, the BAC was below 0.20 g/kg. In these 20 cases, the median time between blood samples was 0.46 h. The empirical calculations of t₁/₂ for cases with declining EtG and EtS concentrations yielded a median of 2.6 h for EtG and 2.4 h for EtS. A strong positive correlation was found between empirical t₁/₂ of EtG and EtS (rs=0.81, p < 0.001). Conclusions The t₁/₂ values for EtG and EtS in apprehended drivers are comparable to those reported in experimental studies. The findings contribute to forensic alcohol assessments and legal expert reports. Additional research is needed to investigate EtG and EtS elimination kinetics in real-life impaired driving scenarios.

• Solhaug, Vigdis; Waade, Ragnhild Birkeland; Jansrud, Lene; Molden, Espen; Størset, Elisabet & Høiseth, Gudrun [Vis alle 7 forfattere av denne artikkelen] (2025). Antipsychotic load during olanzapine mono- versus polytherapy and in relation to age. European Journal of Clinical Pharmacology. ISSN 0031-6970. 82(1). doi: 10.1007/s00228-025-03947-y. Fulltekst i vitenarkiv
• Årnes, Marit; Edvardsen, Hilde Marie Erøy; Holmen, Line Berge; Kristoffersen, Lena & Høiseth, Gudrun (2025). Post-mortem formation of GHB: A retrospective study of forensic autopsies. Forensic Science International. ISSN 0379-0738. 372. doi: 10.1016/j.forsciint.2025.112492. Fulltekst i vitenarkiv Vis sammendrag

  Aims The aims were to investigate the occurrence of post-mortem formation of gammahydroxybutyrate (GHB) at different GHB blood concentration levels, the urine/blood ratios seen after post-mortem formation of GHB, and how often ethanol was co-formed with GHB. Methods Our study includes 525 cases with GHB concentrations above 31.2 mg/L in blood and urine. The results were linked to the Norwegian Cause of Death Registry. We set a ratio below two between urine and blood GHB concentration as indicator for postmortem formation of GHB, and used data regarding official causes of death to verify the classification. Post-mortem formed ethanol was defined as positive ethanol combined with negative ethyl sulfate (EtS) results. Results Of all GHB positive cases, 85 % were defined as post-mortem formation, with a median urine/blood ratio of 0.52. The majority were lower concentrations, but 30 % of the cases showed GHB blood concentrations above approximately 50 mg/L (500 μmol/L). In the cases with urine/blood ratio above two, intake of GHB was suspected, and 15 % of these had GHB concentration in blood below approximately 50 mg/L. Co-formation of ethanol was seen in 27 % of cases with post-mortem formed GHB. The post-mortem interval (PMI) was significantly longer in cases with post-mortem formed GHB and ethanol. Conclusions GHB in post-mortem cases is most commonly formed after death, and concentrations are mainly, but not exclusively, in lower levels. Co-formation of ethanol occurs in about 30 % of cases, and increasing PMI increase the frequency of post-mortem formation of GHB and ethanol.

• Solhaug, Vigdis; Waade, Ragnhild Birkeland; Molden, Espen; Størset, Elisabet; Høiseth, Gudrun & Tveito, Marit (2025). The Effect of Age on Antipsychotic Serum Concentration in Males and Females: A Study Based on Therapeutic Drug Monitoring Data From 19,926 Patients. Therapeutic Drug Monitoring. ISSN 0163-4356. 47(5), s. 662–668. doi: 10.1097/FTD.0000000000001309. Fulltekst i vitenarkiv
• Chalabianloo, Fatemeh; Fadnes, Lars T.; Johansson, Kjell Arne; Høiseth, Gudrun; Vold, Jørn Henrik & Kringen, Marianne K. [Vis alle 8 forfattere av denne artikkelen] (2024). Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 134(3), s. 333–344. doi: 10.1111/bcpt.13975. Fulltekst i vitenarkiv Vis sammendrag

  Background A considerable inter-individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood. Objectives We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration-to-dose ratio (CDR) and discussed the clinical implications of the findings. Methods We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses. Findings A positive association was found between CDR and the homozygous CYP2B6*6 genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations. Conclusions This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes.

• Bakke, Eirin; Nilsen, Mariann; Strand, Dag Helge; Øiestad, Elisabeth Leere & Høiseth, Gudrun (2024). Enantiomer-specific analysis of amphetamine in urine, oral fluid and blood. Journal of Analytical Toxicology. ISSN 0146-4760. 48(5), s. 254–262. doi: 10.1093/jat/bkae038. Fulltekst i vitenarkiv Vis sammendrag

  Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.

• Mørch-Johnsen, Gunhild Heide; Jamt, Ragnhild Elén Gjulem; Fainberg-Sandbu, Jonas Rønningen; Øiestad, Åse Marit Leere & Høiseth, Gudrun (2024). Driving under the influence of cocaine and MDMA: Relationship between blood concentrations and results from clinical test of impairment. Journal of Analytical Toxicology. ISSN 0146-4760. 48(5), s. 380–387. doi: 10.1093/jat/bkae024. Fulltekst i vitenarkiv Vis sammendrag

  The general use of cocaine is increasing in recent years, while the trend for 3,4-methylenedioxymethamphetamine (MDMA) is less clear. The relationship between blood concentrations and impairment is poorly understood, which complicates interpretation. The aims of this study were to report prevalence and blood concentrations of cocaine and MDMA in drugged drivers, and to investigate the relationship between blood concentrations and impairment. Samples of whole blood were collected from apprehended drivers in the period 2000–2022, and a clinical test of impairment (CTI) was simultaneously performed. The samples were initially analyzed for cocaine and MDMA using gas chromatography–mass spectrometry (until 2009 and 2012, respectively), and later using ultra-high-performance liquid chromatography–tandem mass spectrometry. Overall, cocaine was detected in 2,331 cases and MDMA in 2,569 cases. There were 377 and 85 mono cases of cocaine and MDMA, respectively. In the mono cases, the median cocaine concentration was 0.09 mg/L (range: 0.02–1.15 mg/L), and 54% of the drivers were clinically impaired. The median MDMA concentration was 0.19 mg/L (range: 0.04–1.36 mg/L), and 38% were clinically impaired. There was a statistically significant difference in the median cocaine concentration between drivers assessed as not impaired (0.07 mg/L) and drivers assessed as impaired (0.10 mg/L) (P = 0.009). There was also a significant effect of the blood concentration of cocaine (adjusted odds ratio [aOR] = 6.42, 95% confidence interval [CI] = 1.13–36.53, P = 0.036) and driving during the evening/night-time (aOR = 2.17, 95% CI = 1.34–3.51, P = 0.002) on the probability of being assessed as impaired on the CTI. No significant differences were found for MDMA. Many drivers are not assessed as impaired on a CTI following cocaine or especially MDMA use. For cocaine, a relationship between blood concentrations and impairment was demonstrated, but this could not be shown for MDMA.

• Årving, Alexander Braadving; Hilberg, Thor; Vigerust, Elisabeth; Jørgenrud, Benedicte Marie; Bogstrand, Stig Tore & Mørland, Jørg Gustav [Vis alle 7 forfattere av denne artikkelen] (2024). Assessing alcohol consumption across phosphatidylethanol levels using HDL-cholesterol as a predictor. Alcohol and Alcoholism. ISSN 0735-0414. 60(1), s. 1–7. doi: 10.1093/alcalc/agae085. Fulltekst i vitenarkiv Vis sammendrag

  Aims: Prior research has established a correlation between increases of High-Density Lipoprotein Cholesterol (HDL-C) levels and alcohol consumption. This study aimed to explore the association between phosphatidylethanol (PEth) levels and the amount of consumed ethanol, utilizing HDL-C as a surrogate marker on a population level. This endeavor offers an adjunct to other studies. Methods: PEth and HDL-C levels in 50 751 samples from 29 899 patients in Norway were measured simultaneously in whole blood and serum, respectively. Linear mixed model analyses were employed to assess HDL-C levels within different PEth intervals. Drawing on previous research indicating an increase of .0035 mmol/L in HDL-C per gram of pure ethanol consumed per day, and assuming no alcohol intake in the zero PEth group, we estimated mean daily ethanol intake at the group level for males in each PEth interval. Results: Results revealed a significant correlation between PEth and HDL-C levels (Spearman’s rho = .385 for women, .420 for men, P

• Hjelmeland, Knut Johan; Middelkoop, Gerrit; Mørland, Jørg Gustav & Høiseth, Gudrun (2024). The relationship between clinical impairment and blood drug concentration: Comparison between the most prevalent traffic relevant drug groups. Forensic Science International. ISSN 0379-0738. 363. doi: 10.1016/j.forsciint.2024.112180. Fulltekst i vitenarkiv Vis sammendrag

  Aim The aim of the present study was to investigate the relationship between blood concentrations of four different drug classes; ethanol, benzodiazepines, amphetamines and tetrahydrocannabinol (THC) and driver impairment as assessed by a clinical test of impairment (CTI). Methods Data was retrieved from a national database on CTI assessments and accompanying blood drug concentrations from apprehended drivers. All drug concentrations in blood were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and compared to the results of the CTI which were categorized as either “not impaired”, “mildly impaired”, “moderately impaired”, or “considerably impaired”. Results A total number of 15 514 individual mono drug-cases collected over 9 years was included. 89 % were men and the median age was 34 years. In addition, 3 684 individual cases with similar age and gender distribution where no drugs were detected, were included as a reference group. For ethanol and benzodiazepines the percentage of clinically impaired cases increased markedly from lower to higher concentration windows, from 60 % to 97 % for ethanol and from 38 % to 76 % for benzodiazepines. The corresponding increase for amphetamines and THC was modest, from 43 % to 58 % for amphetamines and from 41 % to 55 % for THC. The correlation between drug concentration and degree of impairment was high for ethanol (Spearman´s rho=0.548, p<0.001) and relatively high for benzodiazepines (Spearman´s rho=0.377, p<0.001), but low for amphetamines (Spearman´s rho=0.078, p<0.001) and THC (Spearman´s rho=0.100, p<0.001). Conclusion The percentage of impaired drivers increased with increasing blood drug concentration for all four drug classes, most pronounced for ethanol and benzodiazepines and much less for amphetamines and THC. The median blood drug concentration increased with increasing magnitude of impairment for ethanol and benzodiazepines, while this was much less pronounced for amphetamines and THC. The ranges of drug concentrations, however, were wide for all four drug classes in all impairment categories as assessed by individual clinical examination.

• Holman, Peder Olai Skjeflo; Høiseth, Gudrun; Bachs, Liliana Casulleras; Thaulow, Cecilie Hasselø; Vevelstad, Merete Synnøve Horn & Mørland, Jørg Gustav [Vis alle 7 forfattere av denne artikkelen] (2023). A two-sample approach to retrograde extrapolation of blood THC concentrations – Is it feasible? Forensic Science International. ISSN 0379-0738. 352(111833). doi: 10.1016/j.forsciint.2023.111833. Fulltekst i vitenarkiv Vis sammendrag

  Background Retrograde extrapolation of drug concentrations in blood can be relevant in cases of drug-impaired driving and is regularly used in forensic toxicology in Norway. Δ9-tetrahydrocannabinol (THC) has complex, multi-compartmental pharmacokinetics, which makes retrograde extrapolation of blood THC concentrations problematic. In the present study, we evaluated an approach to retrograde extrapolation in which momentary rates of decrease of THC were estimated from two consecutive blood samples in apprehended drivers. Material and methods Data were collected from apprehended drivers in Norway 2000–2020. We included 548 cases in which THC was detected in two consecutive blood samples collected ≥ 20 min apart. THC concentrations were measured by GC-MS and UHPLC-MS/MS. In each case, THC concentrations and the time between the two sampling points (Δt) were used to estimate the rate constant k. The relationship between THC concentration and k was modelled by linear regression. Results The median Δt was 31 min (interquartile range, IQR = 9). The median blood THC concentration was 2.4 μg/L (IQR = 3.4) at the first sampling point and 2.3 μg/L (IQR =3.1) at the second. The concentration decreased in 62% and increased in 38% of all cases. However, considering measurement uncertainty, the changes were not statistically significant in 87% of cases. The mean of k was 0.12 h-1, corresponding to an apparent t1/2 of 6.0 h. The t1/2 predicted from linear regression of k against THC concentration ranged from 0.93 to 13 h for the highest and lowest concentrations observed (36 and 0.63 μg/L, respectively). The time from driving to blood collection had a median of 1.7 h (IQR = 1.5), and did not correlate with k. Conclusions The apparent t1/2 of THC calculated from the mean of k was 6.0 h, which is shorter than the terminal elimination t1/2 suggested in previous population studies. This indicates that blood samples were often taken during the late distribution phase of THC. Because Δt was short relative to the rates of decrease expected in the late distribution and elimination phases, the underlying true concentration changes related to in vivo pharmacokinetics were small and masked by the relatively larger “false” changes introduced by random analytical and pre-analytical error. Therefore, individual values of k calculated from only two blood samples taken a short time apart are unreliable, and a two-sample approach to retrograde extrapolation of THC cannot be recommended.

• Solhaug, Vigdis; Tveito, Marit; Waade, Ragnhild Birkeland; Høiseth, Gudrun; Molden, Espen & Smith, Robert Løvsletten (2023). Impact of age, sex and cytochrome P450 genotype on quetiapine and N-desalkylquetiapine serum concentrations: A study based on real-world data from 8118 patients. British Journal of Clinical Pharmacology. ISSN 0306-5251. doi: 10.1111/bcp.15849. Fulltekst i vitenarkiv Vis sammendrag

  Aims To investigate the effect of aging, sex and cytochrome P450 (CYP) genotypes on the exposure of quetiapine (QUE) and the pharmacologically active metabolite N ‐desalkylquetiapine (NDQ). Methods Patients with serum concentrations of QUE and NDQ were included retrospectively from a therapeutic drug monitoring service. The outcome measures were concentration:dose (C:D) ratios of QUE and NDQ, and NDQ:QUE metabolic ratio. Linear mixed model analyses were used to evaluate the effects of age, sex and, subsequently, CYP2D6/3A genotypes. Results The average age of the included population ( n  = 8118 patients) was 44 years (13.5% ≥65 years). The C:D ratio of QUE and NDQ gradually increased in patients aged &gt;50 years compared to those aged 18–30 years, with 28 and 29% increase, respectively, for patients aged &gt;70 years ( P  &lt; .001). Compared to males, females had 15% lower QUE C:D ratio and 10% higher C:D ratio of NDQ (both P  &lt; .001). The NDQ:QUE metabolic ratio was 30% higher in females than in males ( P  &lt; .001). For females ≥65 years, the NDQ C:D ratio was 36% higher compared to males &lt;65 years ( P  &lt; .001). A significantly higher NDQ C:D ratio was observed for CYP2D6 intermediate (+7%, P  = .012) and poor (+17%, P  = .001) compared to normal metabolizers. No effects of CYP3A4*22 and CYP3A5*1 allele variants were observed. Conclusion This study shows an increase of the QUE and NDQ exposures during aging. Old age, female sex and CYP2D6 allele variants encoding reduced activity are factors associated with high NDQ exposure. Therefore, females ≥65 years carrying CYP2D6 allele variants encoding reduced activity have the highest risk of dose‐dependent side effects of NDQ during QUE treatment.

• Thaulow, Cecilie Hasselø; Helland, Arne; Kongsgaard, Ulf Erik & Høiseth, Gudrun (2023). Oxycodone, Morphine, and Fentanyl in Patients with Chronic Pain: Proposal of Dose-Specific Concentration Ranges. Therapeutic Drug Monitoring. ISSN 0163-4356. 45(6), s. 777–785. doi: 10.1097/FTD.0000000000001112. Fulltekst i vitenarkiv Vis sammendrag

  Background: Interpreting opioid concentrations is challenging because of the lack of reference ranges. Therefore, the authors aimed to propose dose-specific concentration ranges in serum for oxycodone, morphine, and fentanyl in patients with chronic pain, based on concentration measurements from a large number of patients and supported by theoretical pharmacokinetic calculations and previously published concentrations. Methods: The opioid concentrations in patients undergoing therapeutic drug monitoring (TDM) for various indications (TDM group) and patients with cancer (cancer group) were investigated. Patients were divided based on the daily opioid doses, and the 10th and 90th percentiles of the concentrations in each dose interval were evaluated. In addition, the expected average serum concentrations were calculated for each dose interval based on published pharmacokinetic data, and a targeted literature search for previously reported dose-specific concentrations was performed. Results: The opioid concentrations in 1054 patient samples were included: 1004 in the TDM group and 50 in the cancer group. In total, 607 oxycodone, 246 morphine, and 248 fentanyl samples were evaluated. The authors proposed dose-specific concentration ranges based mainly on 10th–90th percentiles of the concentrations measured in patient samples, whereas the calculated average concentrations and previously published concentrations were used to adjust the ranges. In general, results from calculations and concentrations retrieved from previous literature were within the 10th–90th percentiles of concentrations from patient samples. However, the lowest calculated average concentrations of fentanyl and morphine were below the 10th percentiles of patient samples in all dose groups. Conclusions: The proposed dose-specific ranges may be useful for interpreting steady-state opioid serum concentrations in clinical and forensic settings.

• Strand, Maren; Gjerde, Hallvard & Høiseth, Gudrun (2023). Nystagmus among suspected amphetamine impaired drivers. Journal of Forensic and Legal Medicine. ISSN 1752-928X. 95:102502, s. 1–3. doi: 10.1016/j.jflm.2023.102502. Fulltekst i vitenarkiv Vis sammendrag

  Clinical signs of drug use can be helpful to identify which drug has been consumed. Amphetamine intake has traditionally not been considered to cause nystagmus. The aim of this study was to explore whether there is a relationship between amphetamine use and nystagmus in a population of apprehended drivers in a naturalistic setting. We evaluated drivers suspected of drug-impaired driving where blood samples were collected and a clinical test of impairment (CTI) was performed. Evaluation of nystagmus is one of the CTI subtests. The samples were analysed for alcohol and psychoactive drugs. Cases with a nystagmus test were recorded and amphetamine-only cases were compared with alcohol-only cases and with cases where alcohol or drugs were not detected, respectively. Samples from 507 amphetamine-only cases were compared to 485 alcohol-only cases and 205 drug-negative cases. The median blood amphetamine concentration was 0.37 mg/L and the median alcohol concentration was 1.57 g/kg. The proportion of cases with nystagmus was similar in amphetamine-only cases (21%) and drug-negative controls (25%), p = 0.273, but higher in alcohol-only cases (53%), p < 0.001. No association was found between the blood amphetamine concentration and degree of nystagmus (Spearman's ρ = 0.008, p = 0.860), whereas an association between blood alcohol concentration and degree of nystagmus was demonstrated (ρ = 0.249, p < 0.001). In conclusion, our study did not find that apprehended drivers using amphetamine had more frequently nystagmus than a control group that tested negative for alcohol and drugs, even at high amphetamine concentrations in blood. Hence, nystagmus should not be considered a tool for identifying amphetamine-induced impairment in drivers.

• Strand, Maren; Bleka, Øyvind; Kristoffersen, Lena & Høiseth, Gudrun (2023). Driving under the influence of zopiclone: Elimination between two consecutive blood samples. Forensic Science International. ISSN 0379-0738. 349(111764), s. 1–6. doi: 10.1016/j.forsciint.2023.111764. Fulltekst i vitenarkiv Vis sammendrag

  Aim Zopiclone is a widely used hypnotic drug which is frequently detected in apprehended drivers. For assessments in forensic cases, the elimination half-life (t1/2) of a drug is sometimes important. A t1/2 of 3.5–6.5 h for zopiclone is previously reported in healthy individuals, but different factors like age and drug-interactions can affect the t1/2 of zopiclone. The aim of this study was to describe concentrations of zopiclone and co-ingestion of additional drugs in apprehended drivers, and to investigate the t1/2 of zopiclone based on two consecutive blood samples. Methods Data was collected from apprehended drivers in Norway between 2003 and 2021. All cases where zopiclone was detected were included. In a subset of the material, two consecutive whole blood samples were collected ≥ 20 and < 60 min apart. Concentrations of zopiclone in blood were determined by LC-MS or UHPLC-MS/MS. The elimination and t1/2 of zopiclone was estimated from the concentration change of zopiclone and the time interval between the two consecutive blood samples, under the assumption of first order kinetics. Results The median concentration among all zopiclone positive cases was 0.044 mg/L (IQR 0.070 mg/L) (n = 2401). The most frequent additional drugs detected were ethanol (36%), diazepam (22%), amphetamine (14%) and THC (14%). In zopiclone-only cases (n = 364), the median concentration of zopiclone was 0.066 mg/L (IQR 0.115 mg/L). In 112 cases, two consecutive blood samples were collected. Of these, 28 cases showed increasing concentrations of zopiclone between the two sampling time points. Among the cases in which the concentration decreased (n = 84), the median C1 was 0.048 mg/L (IQR 0.062 mg/L) and the median C2 was 0.043 mg/L (IQR 0.056 mg/L). A Bayesian statistical model was used to obtain the posterior distribution of t1/2. The posterior median of t1/2 was estimated to 3.1 h (IQR=0.39 h) when including only the cases showing decreasing concentrations, and this increased to 3.8 h (IQR=0.52 h) when also including samples showing non outlying increase in concentrations. There was no statistically significant gender difference in the calculated half-lives (two-sided Mann-Whitney U test, p = .525). Conclusions This study showed that zopiclone is frequently detected in apprehended drivers in supra therapeutic concentrations and poly drug cases. The elimination of zopiclone in blood from two consecutive blood samples indicated an apparent t1/2 of between 3.1 and 3.8 h, which is within the lower range of what previous experimental studies on healthy individuals have reported.

• Årving, Alexander Braadving; Hilberg, Thor; Sovershaev, Michael; Bogstrand, Stig Tore & Høiseth, Gudrun (2022). Falsely low phosphatidylethanol may be associated with biomarkers of haemolytic disease. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. doi: 10.1111/bcpt.13814. Fulltekst i vitenarkiv Vis sammendrag

  Aims Falsely lower or even negative phosphatidylethanol (PEth) levels may theoretically be seen in patients with haemolytic diseases, and the present study aimed to elucidate this hypothesis. Methods PEth and carbohydrate-deficient transferrin (CDT) from 9893 serum and whole blood samples were included along with markers of haemolysis (i.e. haptoglobin, HbA1c, reticulocytes, LD and Hb). Cases showing discrepancy between PEth and CDT, that is, a low PEth value and a high CDT value, were considered to be possibly caused by falsely lowered PEth despite high alcohol consumption. These cases (N = 233) were compared to the control group without PEth and CDT mismatch. Results The levels of haptoglobin were significantly lower in the cases showing low PEth and high CDT (estimate = −0.62, p = 0.002). The levels of HbA1c (estimate = −3.26, p = 0.001) and Hb (estimate = −0.507, p < 0.001) were also significantly lower in this group. These findings indicate haemolytic diseases in the low PEth/high CDT group. There were no significant differences for reticulocytes and LD concentrations between the low PEth/high CDT group and the control group. Conclusions These results indicate that falsely low PEth values could be associated with markers of haemolytic diseases, although more research is needed to highlight this further.

• Chalabianloo, Fatemeh; Høiseth, Gudrun; Vold, Jørn Henrik; Johansson, Kjell Arne; Kringen, Marianne K. & Dalgard, Olav [Vis alle 12 forfattere av denne artikkelen] (2022). Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations. Journal of Addictive Diseases. ISSN 1055-0887. 41(1). doi: 10.1080/10550887.2022.2057140. Fulltekst i vitenarkiv Vis sammendrag

  Background: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. Objectives: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. Methods: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016–2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. Results: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: −2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (−0.50; −4.59, 3.59; 0.810). Conclusions: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.

• Tveito, Marit; Høiseth, Gudrun; Haslemo, Tore; Molden, Espen & Smith, Robert Løvsletten (2021). Impact of age and gender on paliperidone exposure in patients after administration of long-acting injectable formulations—an observational study using blood samples from 1223 patients. European Journal of Clinical Pharmacology. ISSN 0031-6970. 77(9), s. 1201–1208. doi: 10.1007/s00228-021-03114-z. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Paliperidone palmitate is an antipsychotic medication available as long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age and gender on paliperidone exposure after administration of LAI formulations. Methods Data on serum concentrations of paliperidone from patients using LAI during were included retrospectively from a therapeutic drug monitoring (TDM) service. Information about dose was obtained from the requisition forms. As a measure of exposure, daily dose-adjusted serum concentration (C/D ratio) was used. Based on initial analysis of C/D ratios versus age, a breaking point close to 50 years was observed, thus deciding the grouping of patients as older (≥50 years) or younger (15–49 years). Linear mixed model analyses, allowing multiple measurements per patients, were used. Results In total, 1223 patients were included, whereof 1158 patients used paliperidone LAI in once-monthly intervals. In these patients (27.9% older), older patients had significantly higher paliperidone C/D ratio than younger patients (+20%, p<0.001). Compared to males, females had higher C/D ratio (+14%; p<0.001). Subsequently, older female users of once-monthly LAI intervals had 41% higher paliperidone C/D ratios compared to younger males (15.0 vs. 21.2 nM/mg; p<0.001). Compared to females aged 21–30 years, females with high age (≥70 years) had at least 105% higher paliperidone C/D ratio (p<0.001). Conclusion The present study shows that older age and female gender are associated with higher paliperidone exposure than younger age and males, respectively. Particularly, older female patients (>50 years) are likely exposed to high concentration and cautious dosing in this subgroup is required.

• Chalabianloo, Fatemeh; Fadnes, Lars T.; Høiseth, Gudrun; Ohldieck, Christian; Vold, Jørn Henrik & Aas, Christer Frode [Vis alle 9 forfattere av denne artikkelen] (2021). Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway. Substance Abuse Treatment, Prevention, and Policy. 16, s. 1–8. doi: 10.1186/s13011-021-00367-w. Fulltekst i vitenarkiv Vis sammendrag

  Background: There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments. Methods: This naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data. Results: The mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p < 0.001); the specific subjective withdrawal symptoms of anxiety (p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049). Conclusions: The findings suggest that the patient’s self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.

• Degerud, Eirik Magnus Meek; Høiseth, Gudrun; Mørland, Jørg; Ariansen, Inger Kristine Holtermann; Graff-Iversen, Sidsel & Ystrøm, Eivind [Vis alle 9 forfattere av denne artikkelen] (2021). Associations of Binge Drinking with the Risks of Ischemic Heart Disease and Stroke: A Study of Pooled Norwegian Health Surveys. American Journal of Epidemiology. ISSN 0002-9262. 190(8), s. 1592–1603. doi: 10.1093/aje/kwab063. Fulltekst i vitenarkiv Vis sammendrag

  Norwegian health survey data (1987 – 2003) were analysed to determine if binge drinking increases the risk of incident major events from ischemic heart disease (IHD) and stroke. Among current drinkers reporting average alcohol intakes between 2 to 60 g/day (n = 44,476), frequent binge drinking (5+ units ≥ once per month) was not associated with a greater risk of IHD (adjusted hazard ratio = 0.91, 95% confidence interval: 0.76, 1.09) nor stroke (adjusted hazard ratio = 0.98, 95% confidence interval: 0.81, 1.19), in comparison with participants who reported that they never or only infrequently (<once per month) had episodes of binge drinking. Participants with an average alcohol intake between 2 – 60 g/day had a lower risk of IHD in comparison with participants with very low intakes (<2 g/day) both among frequent binge drinkers (adjusted hazard ratio = 0.67, 95% confidence interval: 0.56, 0.80) and among never/infrequent binge drinkers (adjusted hazard ratio = 0.75, 95% confidence interval: 0.67, 0.84). The findings suggest that frequent binge drinking does not, independently of the average alcohol intake, increase the risk of incident IHD or stroke events. However, the findings should be interpreted in light of the limitations of the study design.

• Midtlyng, Lena; Høiseth, Gudrun; Luytkis, Hege Cathrine; Kristoffersen, Lena; Nygaard, Ilah Le & Strand, Maren [Vis alle 8 forfattere av denne artikkelen] (2021). Relationship between betahydroxybutyrate (BHB) and acetone concentrations in postmortem blood and cause of death. Forensic Science International. ISSN 0379-0738. 321:110726, s. 1–6. doi: 10.1016/j.forsciint.2021.110726. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Hilberg, Thor; Trydal, Torleif; Husa, Asgeir; Vindenes, Vigdis & Bogstrand, Stig Tore (2021). The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. s. 1–9. doi: 10.1111/bcpt.13662. Fulltekst i vitenarkiv Vis sammendrag

  Background The aim of this study was to evaluate the quantitative relation between common clinical chemical analyses and ethanol use, measured by a combination of the two alcohol markers phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT). Methods Results of PEth and CDT in whole blood and serum, respectively, were included, together with information on 10 different commonly measured clinical chemical analytes, as well as age and sex. PEth was analysed by UPC2-MS/MS and CDT was measured by capillary electrophoresis. Results Samples from 4873 patients were included. The strongest relation to alcohol consumption as measured by PEth, when correcting for age and sex, was found for HDL-C (standardized β = 0.472, p < 0.001), AST (standardized β = 0.372, p < 0.001), ferritin (standardized β = 0.332, p < 0.001) and GGT (standardized β = 0.325, p < 0.001). The relation to PEth was weak for total cholesterol, TG and ALP. No relation was found for Hb and LDL-C. Conclusions When using PEth as a marker for alcohol consumption, this study demonstrated the quantitative relation to commonly used test as AST or GGT, but also an important relation to ferritin or HDL-C. In clinical practice, elevated levels of these clinical chemical analytes should initiate further work-up on possibly harmful alcohol use.

• Tverdal, Aage; Høiseth, Gudrun; Magnus, Per; Næss, Øyvind; Selmer, Randi & Knudsen, Gun Peggy [Vis alle 7 forfattere av denne artikkelen] (2021). Alcohol Consumption, HDL-Cholesterol and Incidence of Colon and Rectal Cancer: A Prospective Cohort Study including 250,010 Participants. Alcohol and Alcoholism. ISSN 0735-0414. 56(6), s. 718–725. doi: 10.1093/alcalc/agab007. Fulltekst i vitenarkiv Vis sammendrag

  Aims:Alcohol consumption has been linked to colorectal cancer (CRC) and also to the high-densitylipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aimof this study was to investigate the association between self-reported alcohol consumption, HDL-Cand incidence of CRC, separately for the two sites. Methods:Altogether, 250,010 participants in Norwegian surveys have been followed-up for anaverage of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up,3023 and 1439 colon and rectal cancers were registered. Results:For men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98–1.12)for colon and 1.08 (1.02–1.15) for rectal cancer. The corresponding figures for women were 1.03(0.97–1.10) and 1.05 (1.00–1.10). There was a positive association between alcohol consumptionand HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62–0.89) per 1 mmol/l)and positively associated with rectal cancer, although not statistically significant (1.15 (0.92–1.44).A robust regression that assigned weights to each observation and exclusion of weights≤0.1increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. Theassociations with rectal cancer remained unchanged. Conclusion:Our results support a positive association between alcohol consumption and colonand rectal cancer, most pronounced for rectal cancer. Considering the positive relation betweenalcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in menremains unsettled.

• Oshaug, Katja; Kronstrand, Robert; Kugelberg, Fredrik C.; Kristoffersen, Lena; Mørland, Jørg Gustav & Høiseth, Gudrun (2021). Frequency of postmortem ethanol formation in blood, urine and vitreous humor – Improving diagnostic accuracy with the use of ethylsulphate and putrefactive alcohols. Forensic Science International. ISSN 0379-0738. 331. doi: 10.1016/j.forsciint.2021.111152. Fulltekst i vitenarkiv Vis sammendrag

  Purpose This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or positive putrefactive alcohols (PA’s) in either medium. Furthermore, it aimed to evaluate the interpretational value of calculated ethanol ratios in relation to EtS and PA results. Methods Blood ethanol positive forensic cases were included; one dataset consisting of 2504 cases with EtS analysed in blood and another dataset with 8001 cases where PA’s were analysed. Results PA’s were found in 24.4% of cases. EtS was negative in 15.3%, 9.4% and 7.4% of cases that were positive for ethanol in blood, urine and vitreous humor, respectively. In EtS negative cases, the concentrations of ethanol in blood, urine and vitreous humor were lower than 0.20 g/kg in 51.3%, 67.4% and 77.8%, respectively. It was 1.0 g/kg or higher in blood in 4.2% of cases. More EtS negative and PA positive cases were seen in central compared to peripheral blood. Ethanol ratios between urine or vitreous humor and blood were significantly lower in both EtS negative and PA positive cases, but large variations were observed. Conclusion EtS and PA analysis improve the diagnostic accuracy of ethanol in postmortem cases. Postmortem ethanol formation in vitreous humor and urine were both more frequent than expected and we recommend the analysis of ethanol primarily in peripheral blood if available.

• Fosen, Jan Toralf; Mørland, Jørg & Høiseth, Gudrun (2020). The relationship between ingested dose of ethanol and amount of ethyl glucuronide formed in blood. Journal of Analytical Toxicology. ISSN 0146-4760. 44(8), s. 861–863. doi: 10.1093/jat/bkaa090. Fulltekst i vitenarkiv Vis sammendrag

  Abstract A positive non-linear relation between the dose of ethanol ingested and the area under the curve (AUC) for ethyl glucuronide (EtG) in urine is previously observed. The relation between both doses and AUC of ethanol and the AUC for EtG in blood is not previously published, and this study aimed to investigate this relationship. After an overnight fast, 10 healthy volunteers ingested 0.5-g ethanol per kilo body weight (low dose) in one occasion and 1.0-g ethanol per kilo body weight (high dose) in the next occasion. Results showed that there was a significant higher median ratio between blood AUC for EtG and dose of ethanol in the high-dose (8.99; range 7.37–10.94) group compared to the low-dose (5.02; range 4.25–6.15) group (P = 0.005). The median ratio between the AUC for EtG and AUC for ethanol was actually significantly higher in the low-dose (1.77; range 1.51–2.24) group compared to the high-dose (1.67; range 1.30–2.02) group (P = 0.005), although values are quite similar. This study therefore showed that the ratio between the AUC for EtG in blood and dose of ethanol is higher after intake of 1.0 g/kg than 0.5 g/kg. This pattern is however not seen when AUC for EtG is compared to AUC for ethanol. Results therefore support that the percentage of ethanol converted to EtG is not increasing when the doses increase. An explanation for the positive non-linear relation previously observed between the dose of ethanol ingested and amount of EtG formed may be a relative higher first-pass metabolism of ethanol at lower doses.

• Andersen, Jannike Mørch; Høiseth, Gudrun & Nygaard, Egil (2020). Prenatal exposure to methadone or buprenorphine and long-term outcomes: A meta-analysis. Early Human Development. ISSN 0378-3782. 143:104997, s. 1–13. doi: 10.1016/j.earlhumdev.2020.104997. Fulltekst i vitenarkiv Vis sammendrag

  Aim To combine meta-analyses of multiple long-term outcomes in children prenatally exposed to methadone or buprenorphine through their mothers' Opioid maintenance therapy (OMT) with a systematic review of similar outcomes in experimental animals. Method The Medline, Embase, Web of Science, CINAHL, Cochrane and Epistemonikos databases were searched through August 30, 2018. Clinical studies measuring effects on cognitive, behavioral or visual outcomes in 3 months or older children prenatally exposed to OMT and control group(s) were included for meta-analyses. Experimental animal studies with similar exposures and outcomes were included in a systematic review. The three authors independently performed abstract screenings and full-text reviews, and extracted the data. One author performed the meta-analyses. Results The pooled results of the meta-analyses showed worse cognitive, psychomotor, behavioral, attentional and executive functioning, and affected vision in children born to mothers who were in OMT during pregnancy compared to children without prenatal drug exposure (overall effect size = 0.49, 95% confidence interval = 0.38, 0.59, p < 0.00001). Many of the experimental animal studies showed impaired outcomes after prenatal exposure to methadone or buprenorphine. The clinical results may be biased, e.g., with the OMT group having more concurrent risk factors than the unexposed comparison group. There are few studies of older children. Conclusion Children born to mothers in OMT show worse outcomes for a number of different behaviors and impaired vision compared to children born to nonusers. Experimental animal studies indicate that there might be a causal relationship between prenatal methadone or buprenorphine exposure and subsequent negative outcomes.

• Årnes, Marit; Bachs, Liliana; Samarrai, Muhammad Al; Jones, Alan Wayne & Høiseth, Gudrun (2020). Rate of elimination of γ-hydroxybutyrate from blood determined by analysis of two consecutive samples from apprehended drivers in Norway. Forensic Science International. ISSN 0379-0738. 314(110374), s. 1–6. doi: 10.1016/j.forsciint.2020.110374. Fulltekst i vitenarkiv
• Årving, Alexander Braadving; Høiseth, Gudrun; Hilberg, Thor; Trydal, Torleif; Husa, Asgeir & Djordjevic, Aleksandar [Vis alle 9 forfattere av denne artikkelen] (2020). Comparison of the Diagnostic Value of Phosphatidylethanol and Carbohydrate-Deficient Transferrin as Biomarkers of Alcohol Consumption. Alcoholism: Clinical and Experimental Research. ISSN 0145-6008. 45(1), s. 153–162. doi: 10.1111/acer.14503. Fulltekst i vitenarkiv Vis sammendrag

  Background The aim of this study was to compare the results of Phosphatidylethanol (PEth) and carbohydrate‐deficient transferrin (CDT) in blood as biomarkers of alcohol consumption in a large clinical cohort and to evaluate concentrations in relation to age and sex. Methods Results of PEth 16:0/18:1 in blood and CDT in serum were included, together with information of age and sex, which were extracted from a clinical chemistry database containing samples mostly from patients of primary care physicians and social care institutions. PEth concentrations were determined using Ultra Performance Convergence chromatography mass spectrometer. CDT was quantified by electrophoretic Capillary System. CDT values ≥ 1.7 %‐units and PEth values ≥ 0.31 µmol/L were considered to indicate heavy alcohol consumption. Results Samples from 6705 patients were included. The median age was 54.5 years, and 34 % were females. Only 47 % of the patients with PEth ≥ 0.31 µmol/L had increased CDT ≥ 1.7 %‐units examined in the same specimen (Cohen’s kappa was 0.43, p < 0.001). Patients above 50 years had significantly higher concentrations for both CDT (1.0 %‐units vs. 0.9 %‐units, p < 0.001) and PEth (0.340 µmol/L vs. 0.200 µmol/L, p < 0.001) compared with younger patients. Concentrations of CDT were significantly higher in males compared with females (p = 0.002), while no significant sex differences were seen for PEth (p = 0.465). Conclusions A high fraction of the patients had PEth values above the suggested cutoff for heavy drinking and normal CDT values, verifying the superior sensitivity of PEth compared with CDT. The effect of age seems to be minor for both markers. Higher concentrations of CDT, but not PEth, were seen in males, indicating that PEth, as opposed to CDT, might be formed equally in men and women. Therefore, the bias due to sex is possibly present only for CDT, not for PEth.

• Waade, Ragnhild Birkeland; Solhaug, Vigdis & Høiseth, Gudrun (2020). Impact of CYP2D6 on serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol. British Journal of Clinical Pharmacology. ISSN 0306-5251. 00(0), s. 1–8. doi: 10.1111/bcp.14626. Fulltekst i vitenarkiv Vis sammendrag

  Aims To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose‐adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose‐adjusted serum concentrations in the perphenazine‐treated patients. Methods Serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP‐genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose‐adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. Results Mean dose‐adjusted serum concentrations of perphenazine (564 samples) were 3.9‐fold and 1.6‐fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .001 and P < .01). For zuclopenthixol (658 samples), mean dose‐adjusted serum concentrations were about 1.5‐fold and 1.3‐fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .01 and P < .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose‐adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). Conclusions This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and flupentixol. The CYP2D6*41 allele appears to have a reduced function close to nonfunctional variant alleles.

• Bakke, Eirin; Høiseth, Gudrun; Furuhaugen, Håvard; Berg, Thomas; Arnestad, Marianne & Gjerde, Hallvard (2020). Oral fluid to blood concentration ratios of different psychoactive drugs in samples from suspected drugged drivers. Therapeutic Drug Monitoring. ISSN 0163-4356. 42(5), s. 795–800. doi: 10.1097/FTD.0000000000000760. Fulltekst i vitenarkiv
• Mørch-Johnsen, Gunhild Heide; Høiseth, Gudrun; Middelkoop, Gerrit & Øiestad, Åse Marit Leere (2020). Blood concentrations of designer benzodiazepines: relation to impairment and findings in forensic cases. Journal of Analytical Toxicology. ISSN 0146-4760. 44(8), s. 905–914. doi: 10.1093/jat/bkaa043. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Hjelmeland, Knut Johan & Mørland, Jørg (2020). A comparison of driving related skills impaired by ethanol and zopiclone. Traffic Injury Prevention. ISSN 1538-9588. 22(1), s. 26–31. doi: 10.1080/15389588.2020.1849643. Fulltekst i vitenarkiv
• Degerud, Eirik Magnus Meek; Høiseth, Gudrun; Mørland, Jørg Gustav; Ariansen, Inger; Graff-Iversen, Sidsel & Ystrøm, Eivind [Vis alle 8 forfattere av denne artikkelen] (2020). Association of coincident self-reported mental health problems and alcohol intake with all-cause and cardiovascular disease mortality: A Norwegian pooled population analysis. PLoS Medicine. ISSN 1549-1277. 17(2), s. 1–21. doi: 10.1371/journal.pmed.1003030. Fulltekst i vitenarkiv Vis sammendrag

  Background The disease burden attributable to mental health problems and to excess or harmful alcohol use is considerable. Despite a strong relationship between these 2 important factors in population health, there are few studies quantifying the mortality risk associated with their co-occurrence in the general population. The aim of this study was therefore to investigate cardiovascular disease (CVD) and all-cause mortality according to self-reported mental health problems and alcohol intake in the general population. Methods and findings We followed 243,372 participants in Norwegian health surveys (1994–2002) through 2014 for all-cause and CVD mortality by data linkage to national registries. The mean (SD) age at the time of participation in the survey was 43.9 (10.6) years, and 47.8% were men. During a mean (SD) follow-up period of 16.7 (3.2) years, 6,587 participants died from CVD, and 21,376 died from all causes. Cox models estimated hazard ratios (HRs) with 95% CIs according to a mental health index (low, 1.00–1.50; high, 2.01–4.00; low score is favourable) based on the General Health Questionnaire and the Hopkins Symptom Checklist, and according to self-reported alcohol intake (low, <2; light, 2–11.99; moderate, 12–23.99; high, ≥24 grams/day). HRs were adjusted for age, sex, educational level, marital status, and CVD risk factors. Compared to a reference group with low mental health index score and low alcohol intake, HRs (95% CIs) for all-cause mortality were 0.93 (0.89, 0.97; p = 0.001), 1.00 (0.92, 1.09; p = 0.926), and 1.14 (0.96, 1.35; p = 0.119) for low index score combined with light, moderate, and high alcohol intake, respectively. HRs (95% CIs) were 1.22 (1.14, 1.31; p < 0.001), 1.24 (1.15, 1.33; p < 0.001), 1.43 (1.23, 1.66; p < 0.001), and 2.29 (1.87, 2.80; p < 0.001) for high index score combined with low, light, moderate, and high alcohol intake, respectively. For CVD mortality, HRs (95% CIs) were 0.93 (0.86, 1.00; p = 0.058), 0.90 (0.76, 1.07; p = 0.225), and 0.95 (0.67, 1.33; p = 0.760) for a low index score combined with light, moderate, and high alcohol intake, respectively, and 1.11 (0.98, 1.25; p = 0.102), 0.97 (0.83, 1.13; p = 0.689), 1.01 (0.71, 1.44; p = 0.956), and 1.78 (1.14, 2.78; p = 0.011) for high index score combined with low, light, moderate, and high alcohol intake, respectively. HRs for the combination of a high index score and high alcohol intake (HRs: 2.29 for all-cause and 1.78 for CVD mortality) were 64% (95% CI 53%, 74%; p < 0.001) and 69% (95% CI 42%, 97%; p < 0.001) higher than expected for all-cause mortality and CVD mortality, respectively, under the assumption of a multiplicative interaction structure. A limitation of our study is that the findings were based on average reported intake of alcohol without accounting for the drinking pattern. Conclusions In the general population, the mortality rates associated with more mental health problems and a high alcohol intake were increased when the risk factors occurred together.

• Tveito, Marit; Smith, Robert Løvsletten; Molden, Espen & Høiseth, Gudrun (2020). Impact of age and CYP2D6 genotype on exposure of zuclopenthixol in patients using long-acting injectable versus oral formulation-an observational study including 2044 patients. European Journal of Clinical Pharmacology. ISSN 0031-6970. 77, s. 215–221. doi: 10.1007/s00228-020-03002-y. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Zuclopenthixol is an antipsychotic available as oral and long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age on zuclopenthixol exposure during oral and LAI administrations without and with adjustment for CYP2D6 genotype. Methods Data on serum concentrations of zuclopenthixol and CYP2D6 genotype (available for 28.2% of the population) from patients using oral or LAI zuclopenthixol were included retrospectively from a therapeutic drug monitoring service during the period 2005–2019. As a measure of exposure, dose-adjusted serum concentration (C/D ratio) was used. Based on age, patients were grouped to older (≥ 65 years) or younger (18–64 years). Linear mixed model analyses without and with adjustment for CYP2D6 genotype were used. Results Serum concentrations of zuclopenthixol from 1145 (14.1% older) and 899 patients (24.6% older) in the LAI and oral groups were included, respectively. Compared with younger patients, older patients had a higher C/D ratio of zuclopenthixol for LAI (+ 25–33%, p < 0.001) and oral formulation (+ 25–29%, p ≤ 0.003) without and with adjustment for CYP2D6 genotype. The doses were lower in older versus younger patients (oral: − 30%; LAI: − 20%; p < 0.001). Compared with the younger LAI users without reduced CYP2D6 function, a higher C/D ratio was observed in the older LAI users with reduced CYP2D6 function (+ 104%, p < 0.001). Conclusion The present study showed that zuclopenthixol exposure increases in older patients and that the older LAI users with reduced CYP2D6 function are exposed to high serum concentrations. Also, the present study showed that similar dose reductions are required for oral and LAI users.

• Høiseth, Gudrun; Nilsson, Gunnel H.; Lundberg, Rickard; Forsman, Malin; Kronstrand, Christoffer & Nyström, Ingrid [Vis alle 12 forfattere av denne artikkelen] (2020). Evaluating the hip-flask defence using analytical data from ethanol and ethyl glucuronide. A comparison of two models. Forensic Science International. ISSN 0379-0738. 316:110409, s. 1–8. doi: 10.1016/j.forsciint.2020.110409. Fulltekst i vitenarkiv Vis sammendrag

  Aim Claimed intake of alcohol after a traffic incident, called the hip-flask defence, can be objectively assessed by different methods. One of them is the use of two consecutive ethanol concentrations in urine and the ratio between ethanol concentrations in urine and blood. Another one is the concentrations of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in blood and their ratio to ethanol. The experimental basis for both these models is from single dose studies only. The aim of this study was therefore to describe the kinetics of ethanol, EtG and EtS after ingestion of two repeated doses of ethanol and to investigate the usefulness of the different models for the assessment of the hip-flask defence. Methods Thirty-five subjects ingested a first dose of 0.51 g of ethanol per kilo body weight, and two hours later a second dose (the hip-flask drink) of 0.25, 0.51 or 0.85 g of ethanol per kilo body weight. Ten urine and 17 blood samples were collected and analysed for ethanol, EtG and EtS using fully validated methods. It was investigated if all subjects fulfilled the criteria for recent drinking, according to the two different models, when using the samples collected 180–240 minutes after start of first dose drinking. According to the first model, increase in urinary ethanol concentrations and a ratio UAC/BAC below 1.3 indicated recent drinking. According to the second model, increase in blood EtG concentrations and a ratio ethanol (g/kg)/EtG (mg/L) above 1 indicated recent drinking. Results All subjects in the high dose group fulfilled all criteria for recent drinking. One subject in the medium dose group and nine subjects in the low dose group failed to show increasing UAC and/or a UAC/BAC ratio below 1.3. One subject in the low dose group failed to show increasing concentrations of blood EtG, but all subjects showed a ratio ethanol/EtG above 1. Conclusions The present study showed, by the use of experimental data, that both two models used to investigate the hip-flask defence can be used, but only when the hip-flask dose is sufficiently high.

• Tveito, Marit; Molden, Espen; Høiseth, Gudrun; Correll, Christoph U. & Smith, Robert Løvsletten (2019). Impact of age and CYP2D6 genetics on exposure of aripiprazole and dehydroaripiprazole in patients using long-acting injectable versus oral formulation: relevance of poor and intermediate metabolizer status. European Journal of Clinical Pharmacology. ISSN 0031-6970. 76, s. 41–49. doi: 10.1007/s00228-019-02768-0. Fulltekst i vitenarkiv
• Tveito, Marit; Handal, Marte; Engedal, Knut; Smith, Robert Løvsletten; Høiseth, Gudrun & Skurtveit, Svetlana (2019). Forskrivning av antipsykotika til hjemmeboende eldre 2006–18. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(16), s. 1554–1558. doi: 10.4045/tidsskr.19.0233. Fulltekst i vitenarkiv
• Kongsgaard, Ulf & Høiseth, Gudrun (2019). Dynamic assessment of the pupillary reflex in patients on high-dose opioids. Scandinavian Journal of Pain. ISSN 1877-8860. 19(3), s. 465–471. doi: 10.1515/sjpain-2019-0032. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Pupil size and reaction are influenced by opioids, an effect that is not considered to be affected by opioid tolerance. As clinicians have observed patients on high-dose opioids who exhibited seemingly normal pupil sizes, we wanted to dynamically assess the pupillary reflex in cancer patients on high-dose opioids. Methods We performed a dynamic assessment of the pupillary reflex in cancer patients on high-dose opioids and a control group of healthy volunteers using a portable, monocular, infrared pupillometer. We also performed a clinical examination and measured blood concentrations of opioids and their active metabolites. Results Sixty three patients who were on opioids for 2 months (median time) and on an oral morphine equivalent dose of 250 mg (median dose) were investigated. Most patients used more than one opioid. When correcting for age, pupil size in the group that had received no increase of opioid dose over the last 14 days was not significantly different from pupil size in the healthy volunteer group (p = 0.76), while the group that had increased the dose of opioids differed significantly from healthy volunteers (p = 0.006). We found no statistically significant correlation between total oral morphine equivalents and pupillary reactions or between blood opioid or opioid metabolite concentrations and baseline pupillary changes. Conclusion Pupillary changes do take place in patients on opioids. However, tolerance to these changes occurs when medication is not increased over time. Dynamic pupillometry can give additional information about the degree of tolerance to opioids. Implications These findings elucidate previous misconceptions regarding pupillary effects and tolerance to opioids.

• Bruun, Lina Dorthea; Kjeldstadli, Kari Grandaunet; Temte, Vidar; Birdal, Morris; Bachs, Liliana & Langødegård, Marit [Vis alle 10 forfattere av denne artikkelen] (2019). Detection Time of Oxazepam and Zopiclone in Urine and Oral Fluid after Experimental Oral Dosing. Journal of Analytical Toxicology. ISSN 0146-4760. 43(5), s. 369–377. doi: 10.1093/jat/bky083. Fulltekst i vitenarkiv
• Tveito, Marit; Smith, Robert Løvsletten; Høiseth, Gudrun & Molden, Espen (2019). The Effect of Valproic Acid on Olanzapine Serum Concentration: A Study Including 2791 Patients Treated With Olanzapine Tablets or Long-Acting Injections. Journal of Clinical Psychopharmacology. ISSN 0271-0749. 39(6), s. 561–566. doi: 10.1097/JCP.0000000000001126. Fulltekst i vitenarkiv
• Bakke, Eirin; Høiseth, Gudrun; Arnestad, Marianne & Gjerde, Hallvard (2019). Detection of Drugs in Simultaneously Collected Samples of Oral Fluid and Blood. Journal of Analytical Toxicology. ISSN 0146-4760. 43(3), s. 228–232. doi: 10.1093/jat/bky079. Fulltekst i vitenarkiv
• Temte, Vidar; Kjeldstadli, Kari Grandaunet; Bruun, Lina Dorthea; Birdal, Morris; Bachs, Liliana & Karinen, Ritva Anneli [Vis alle 9 forfattere av denne artikkelen] (2019). An Experimental Study of Diazepam and Alprazolam Kinetics in Urine and Oral Fluid Following Single Oral Doses. Journal of Analytical Toxicology. ISSN 0146-4760. 43(2), s. 104–111. doi: 10.1093/jat/bky062. Fulltekst i vitenarkiv
• Tveito, Marit; Smith, Robert Løvsletten; Molden, Espen; Haslemo, Tore; Refsum, Helge & Hartberg, Cecilie Bhandari [Vis alle 8 forfattere av denne artikkelen] (2018). Age Impacts Olanzapine Exposure Differently During Use of Oral Versus Long-Acting Injectable Formulations: An Observational Study Including 8,288 Patients. Journal of Clinical Psychopharmacology. ISSN 0271-0749. 38(6), s. 570–576. doi: 10.1097/JCP.0000000000000961. Fulltekst i vitenarkiv
• Thaulow, Cecilie Hasselø; Øiestad, Åse Marit Leere; Rogde, Sidsel; Karinen, Ritva Anneli; Brochmann, Gerd-Wenche & Andersen, Jannike Mørch [Vis alle 13 forfattere av denne artikkelen] (2018). Metabolites of heroin in several different post-mortem matrices. Journal of Analytical Toxicology. ISSN 0146-4760. 42(5), s. 311–320. doi: 10.1093/jat/bky002. Fulltekst i vitenarkiv
• Krpo, Maja; Luytkis, Hege Cathrine; Haneborg, An-Magritt & Høiseth, Gudrun (2018). A fatal blood concentration of 5-APB. Forensic Science International. ISSN 0379-0738. 291, s. e1–e3. doi: 10.1016/j.forsciint.2018.08.044. Fulltekst i vitenarkiv
• Havig, Stine Marie; Lea, Dordi; Krpo, Maja; Skari, Ragnhild Margrete; Gustavsen, Ingebjørg G. & Høiseth, Gudrun (2018). Fatal Adverse Event with Dabigatran in Elderly Patient with Reduced Kidney Function. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 123(2), s. 221–226. doi: 10.1111/bcpt.12985. Fulltekst i vitenarkiv
• Degerud, Eirik; Ariansen, Inger Kristine Holtermann; Ystrøm, Eivind; Graff-Iversen, Sidsel; Høiseth, Gudrun & Mørland, Jørg [Vis alle 8 forfattere av denne artikkelen] (2018). Life course socioeconomic position, alcohol drinking patterns in midlife, and cardiovascular mortality: Analysis of Norwegian population-based health surveys. PLoS Medicine. ISSN 1549-1277. 15(1). doi: 10.1371/journal.pmed.1002476. Fulltekst i vitenarkiv Vis sammendrag

  Background: Socioeconomically disadvantaged groups tend to experience more harm from the same level of exposure to alcohol as advantaged groups. Alcohol has multiple biological effects on the cardiovascular system, both potentially harmful and protective. We investigated whether the diverging relationships between alcohol drinking patterns and cardiovascular disease (CVD) mortality differed by life course socioeconomic position (SEP). Methods and findings: From 3 cohorts (the Counties Studies, the Cohort of Norway, and the Age 40 Program, 1987–2003) containing data from population-based cardiovascular health surveys in Norway, we included participants with self-reported information on alcohol consumption frequency (n = 207,394) and binge drinking episodes (≥5 units per occasion, n = 32,616). We also used data from national registries obtained by linkage. Hazard ratio (HR) with 95% confidence intervals (CIs) for CVD mortality was estimated using Cox models, including alcohol, life course SEP, age, gender, smoking, physical activity, body mass index (BMI), systolic blood pressure, heart rate, triglycerides, diabetes, history of CVD, and family history of coronary heart disease (CHD). Analyses were performed in the overall sample and stratified by high, middle, and low strata of life course SEP. A total of 8,435 CVD deaths occurred during the mean 17 years of follow-up. Compared to infrequent consumption (<once/month), moderately frequent consumption (2–3 times per week) was associated with a lower risk of CVD mortality (HR = 0.78, 95% CI 0.72, 0.84) overall. HRs for the high, middle, and low strata of SEP were 0.66 (95% CI 0.58, 0.76), 0.87 (95% CI 0.78, 0.97), and 0.79 (95% CI 0.64, 0.98), respectively, compared with infrequent users in each stratum. HRs for effect modification were 1.30 (95% CI 1.10, 1.54, p = 0.002; middle versus high), 1.23 (95% CI 0.96, 1.58, p = 0.10; low versus high), and 0.96 (95% CI 0.76, 1.21, p = 0.73; low versus middle). In the group with data on binge drinking, 2,284 deaths (15 years) from CVDs occurred. In comparison to consumers who did not binge during the past year, HRs among frequent bingers (≥1 time per week) were 1.58 (95% CI 1.31, 1.91) overall, and 1.22 (95% CI 0.84, 1.76), 1.71 (95% CI 1.31, 2.23), and 1.85 (95% CI 1.16, 2.94) in the strata, respectively. HRs for effect modification were 1.36 (95% CI 0.87, 2.13, p = 0.18; middle versus high), 1.63 (95% CI 0.92, 2.91, p = 0.10; low versus high), and 1.32 (95% CI 0.79, 2.20, p = 0.29; low versus middle). A limitation of this study was the use of a single measurement to reflect lifetime alcohol consumption. Conclusions: Moderately frequent consumers had a lower risk of CVD mortality compared with infrequent consumers, and we observed that this association was more pronounced among participants with higher SEP throughout their life course. Frequent binge drinking was associated with a higher risk of CVD mortality, but it was more uncertain whether the risk differed by life course SEP. It is unclear if these findings reflect differential confounding of alcohol consumption with health-protective or damaging exposures, or differing effects of alcohol on health across socioeconomic groups.

• Høiseth, Gudrun; Arnestad, Marianne; Karinen, Ritva Anneli; Morini, Luca; Rogde, Sidsel & Sempio, Cristina [Vis alle 8 forfattere av denne artikkelen] (2018). Is Hair Analysis Useful in Postmortem Cases? Journal of Analytical Toxicology. ISSN 0146-4760. 42(1), s. 49–54. doi: 10.1093/jat/bkx077. Fulltekst i vitenarkiv
• Thaulow, Cecilie Hasselø; Øiestad, Åse Marit Leere; Rogde, Sidsel; Andersen, Jannike Mørch; Høiseth, Gudrun & Handal, Marte [Vis alle 8 forfattere av denne artikkelen] (2018). Can measurements of heroin metabolites in post-mortem matrices other than peripheral blood indicate if death was rapid or delayed? Forensic Science International. ISSN 0379-0738. 290, s. 121–128. doi: 10.1016/j.forsciint.2018.06.041. Fulltekst i vitenarkiv
• Fosen, Jan Toralf; Høiseth, Gudrun; Sempio, Cristina; Giarratana, Nefele; Enger, Asle & Mørland, Jørg [Vis alle 7 forfattere av denne artikkelen] (2018). Hair EtG: Alterations in segment levels accompanying hair growth. Drug Testing and Analysis. ISSN 1942-7603. 11, s. 112–118. doi: 10.1002/dta.2474. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Austdal, Linn Engeset; Wiik, Elisabeth; Bogstrand, Stig Tore & Mørland, Jørg (2017). Prevalence and concentrations of drugs in older suspected drugged drivers. Traffic Injury Prevention. ISSN 1538-9588. 18(3), s. 231–236. doi: 10.1080/15389588.2016.1247209. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Berg-Hansen, Grim Otto; Øiestad, Åse Marit Leere; Bachs, Liliana Casulleras & Mørland, Jørg (2017). Impairment due to alcohol, tetrahydrocannabinol, and benzodiazepines in impaired drivers compared to experimental studies. Traffic Injury Prevention. ISSN 1538-9588. 18(3), s. 244–250. doi: 10.1080/15389588.2016.1201205. Fulltekst i vitenarkiv
• Mørch-Johnsen, Gunhild Heide; Hjelmeland, Knut Johan; Brochmann, Gerd-Wenche; Karinen, Ritva Anneli & Høiseth, Gudrun (2017). The Appearance, Taste, and Concentrations of Zolpidem Dissolved in Still Water and Carbonated Beverages. Journal of Forensic Sciences. ISSN 0022-1198. doi: 10.1111/1556-4029.13604. Fulltekst i vitenarkiv
• Karinen, Ritva Anneli & Høiseth, Gudrun (2017). A literature review of blood concentrations of new psychoactive substances classified as phenethylamines, aminoindanes, arylalkylamines, arylcyclohexylamines, and indolalkylamines. Forensic Science International. ISSN 0379-0738. 276, s. 120–125. doi: 10.1016/j.forsciint.2017.02.024. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Gottås, André; Berg, Thomas; Arnestad, Marianne; Halvorsen, Per Steinar & Bachs, Liliana Casulleras (2017). Urinary kinetics of heroin metabolites in pigs shortly after intake. Journal of Analytical Toxicology. ISSN 0146-4760. 41(5), s. 451–454. doi: 10.1093/jat/bkx017. Fulltekst i vitenarkiv
• Kringen, Marianne K.; Chalabianloo, Fatemeh; Bernard, Jean-Paul Anthony; Bramness, Jørgen Gustav; Molden, Espen & Høiseth, Gudrun (2017). Combined Effect of CYP2B6 Genotype and Other Candidate Genes on a Steady-State Serum Concentration of Methadone in Opioid Maintenance Treatment. Therapeutic Drug Monitoring. ISSN 0163-4356. 39(5), s. 550–555. doi: 10.1097/FTD.0000000000000437. Fulltekst i vitenarkiv
• Hjelmeland, Knut Johan; Gustavsen, Ingebjørg G.; Øiestad, Elisabeth Leere; Øiestad, Åse Marit Leere; Høiseth, Gudrun & Mørland, Jørg (2017). Zopiclone concentrations in oral fluid and blood after, administration of therapeutic doses of zopiclone. Forensic Science International. ISSN 0379-0738. 278, s. 177–183. doi: 10.1016/j.forsciint.2017.07.004. Fulltekst i vitenarkiv
• Havig, Stine Marie; Høiseth, Gudrun; Strand, Maren; Karinen, Ritva Anneli; Brochmann, Gerd-Wenche & Strand, Dag Helge [Vis alle 8 forfattere av denne artikkelen] (2017). THC and CBD in blood samples and seizures in Norway: Does CBD affect THC-induced impairment in apprehended subjects? Forensic Science International. ISSN 0379-0738. 276, s. 12–17. doi: 10.1016/j.forsciint.2017.04.006. Fulltekst i vitenarkiv
• Fosen, Jan Toralf; Morini, Luca; Sempio, Cristina; Giarratana, Nefele; Enger, Asle & Mørland, Jørg [Vis alle 7 forfattere av denne artikkelen] (2017). Ethyl glucuronide elimination kinetics in fingernails and comparison to levels in hair. Alcohol and Alcoholism. ISSN 0735-0414. 52(5), s. 580–586. doi: 10.1093/alcalc/agx035. Fulltekst i vitenarkiv
• Tveito, Marit; Correll, Christoph U.; Bramness, Jørgen Gustav; Engedal, Knut; Lorentzen, Bernhard & Refsum, Helge [Vis alle 7 forfattere av denne artikkelen] (2016). Correlates of major medication side effects interfering with daily performance: Results from a cross-sectional cohort study of older psychiatric patients. International Psychogeriatrics. ISSN 1041-6102. 28(2), s. 331–340. doi: 10.1017/S1041610215001544. Fulltekst i vitenarkiv Vis sammendrag

  Background: Polypharmacy is common among older persons who are also vulnerable to side effects. We aimed to characterize patients who on admission to a geriatric psychiatric hospital had major medication side effects interfering with daily performance. Methods: Cross-sectional cohort study of patients consecutively admitted to a geriatric psychiatric hospital from 2006, 06 December to 2008, 24 October. The UKU side effect rating scale was performed, and patients were divided into those with no/minor side effects versus those with major side effects. Blood levels of 56 psychotropic drugs and 27 safety laboratory tests were measured upon admission. Results: Of 206 patients included in the analysis, 70 (34%) had major side effects related to drug treatment. The most frequent side effects were asthenia (31%), reduced salivation (31%), concentration difficulties (28%), memory impairment (24%), and orthostatic dizziness (18%). The significant characteristics predicting major side effects were female gender (OR = 2.4, 95% confidence interval (CI) = 1.1–5.5), main diagnosis of affective disorder (OR = 4.3, 95% CI = 1.5–12.3), unreported use of psychotropic medications (OR = 2.0, 95% CI = 1.0–4.1), a higher number of reported psychotropic medications (OR = 1.7, 95% CI = 1.2–2.3), a higher number of reported medications for somatic disorders (OR = 1.2, 95% CI = 1.1–1.5), and a higher score on the Charlson comorbidity index (OR = 1.2, 95% CI = 1.0–1.4) (r2 = 0.238, p < 0.001). Conclusions: Clinicians should be especially aware of side effects related to drug treatment in geriatric psychiatric female patients with a high use of psychotropic and other medications and somatic comorbidity. Unreported use of psychotropic medications was also related to the risk for side effects, and clinicians should make an effort to ascertain all medications taken by geriatric psychiatric patients.

• Høiseth, Gudrun; Tuv, Silja Skogstad & Karinen, Ritva Anneli (2016). Blood concentrations of new designer benzodiazepines in forensic cases. Forensic Science International. ISSN 0379-0738. 268, s. 35–38. doi: 10.1016/j.forsciint.2016.09.006. Fulltekst i vitenarkiv Vis sammendrag

  INTRODUCTION: A number of new designer benzodiazepines have reached the illegal drug market over the past years. Toxicological interpretation of concentrations of these drugs in blood is quite challenging as very limited human data have previously been published. The aim of this study was to report blood concentrations of new designer benzodiazepines in a population of drugged drivers as well as some other criminal offenders, and to relate this to clinical impairment. METHODS: The present material represents cases involving new designer benzodiazepines (clonazolam, diclazepam, flubromazepam, flubromazolam and pyrazolam) and etizolam, submitted for analyses during the period July 1, 2013-May 31, 2016. Analyses were performed using an ultra-performance liquid chromatography-tandem mass spectrometry method. Blood concentrations and results from the clinical test of impairment are reported. RESULTS: New designer benzodiazepines were detected in 77 cases during the study period. The median (range) concentrations were 0.012mg/L (0.00048-0.10) for flubromazolam (n=25), 0.055mg/L (0.0047-1.2) for flubromazepam (n=24), 0.013mg/L (0.0021-0.057) for diclazepam (n=15), 0.050mg/L (0.019-0.17) for etizolam (n=14), 0.0053mg/L (0.0019-0.011) for clonazolam (n=7) and 0.074mg/L for pyrazolam (n=1). In six cases, designer benzodiazepines were the only drugs detected in blood, and in two of those cases, the physician had given the conclusion of "considerably impaired" upon performing the clinical test for impairment. CONCLUSION: Given the lack of previously published data on human concentrations, results presented in this study could be helpful in interpretation of blood concentrations of new designer benzodiazepines. This is crucial for the assessment of the importance of toxicological results in suspected drugged drivers, rape victims, etc.

• Magnus, Per; Birke, Charlotte; Vejrup, Kristine; Haugan, Anita; Alsaker, Elin Hilde Roti & Daltveit, Anne Kjersti [Vis alle 15 forfattere av denne artikkelen] (2016). Cohort Profile Update: The Norwegian Mother and Child Cohort Study (MoBa). International Journal of Epidemiology. ISSN 0300-5771. 45(2), s. 382–388. doi: 10.1093/ije/dyw029. Fulltekst i vitenarkiv
• Fosen, Jan Toralf; Morini, Luca; Sempio, Cristina; Ganss, Rudiger; Mørland, Jørg & Høiseth, Gudrun (2016). Levels of Hair Ethyl Glucuronide in Patients with Decreased Kidney Function: Possibility of Misclassification of Social Drinkers. Alcoholism: Clinical and Experimental Research. ISSN 0145-6008. 40(3), s. 451–456. doi: 10.1111/acer.12970. Fulltekst i vitenarkiv
• Gottås, André; Arnestad, Marianne; Halvorsen, Per Steinar; Bachs, Liliana Casulleras & Høiseth, Gudrun (2016). Pharmacokinetics of heroin and its metabolites in vitreous humor and blood in a living pig model. Forensic Toxicology. ISSN 1860-8965. 34, s. 277–285. doi: 10.1007/s11419-016-0315-z. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Wiik, Elisabeth; Kristoffersen, Lena & Mørland, Jørg (2016). Ethanol elimination rates at low concentrations based on two consecutive blood samples. Forensic Science International. ISSN 0379-0738. 266, s. 191–196. doi: 10.1016/j.forsciint.2016.05.039. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Fosen, Jan Toralf; Liane, Veronica Horpestad; Bogstrand, Stig Tore & Mørland, Jørg (2015). Alcohol Hangover as a Cause of Impairment in Apprehended Drivers. Traffic Injury Prevention. ISSN 1538-9588. 16(4), s. 323–328. doi: 10.1080/15389588.2014.938324. Fulltekst i vitenarkiv
• Karinen, Ritva Anneli; Høiseth, Gudrun; Svendsen, Kristin Opsal; Rogde, Sidsel & Vindenes, Vigdis (2015). A fatal intoxication with phenazone (antipyrine). Forensic Science International. ISSN 0379-0738. 248, s. e13–e15. doi: 10.1016/j.forsciint.2015.01.001. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Haslemo, Tore; Uthus, Linda Hårstad & Molden, Espen (2015). Effect of CYP2B6*6 on steady-state serum concentrations of bupropion and hydroxybupropion in psychiatric patients: A study based on therapeutic drug monitoring data. Therapeutic Drug Monitoring. ISSN 0163-4356. 37(5), s. 589–593. doi: 10.1097/FTD.0000000000000183. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Berg-Hansen, Grim Otto & Mørland, Jørg (2015). Evaluation of the hip-flask defence by determination of ethyl glucuronide and ethyl sulphate concentrations in blood. Forensic Science International. ISSN 0379-0738. 257, s. 398–402. doi: 10.1016/j.forsciint.2015.10.017. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Middelkoop, Gerrit; Mørland, Jørg & Gjerde, Hallvard (2015). Has previous abuse of flunitrazepam been replaced by clonazepam? European Addiction Research. ISSN 1022-6877. 21(4), s. 217–221. doi: 10.1159/000377628. Fulltekst i vitenarkiv
• Tveito, Marit; Lorentzen, Bernhard; Engedal, Knut; Tanum, Lars; Bramness, Jørgen Gustav & Refsum, Helge [Vis alle 7 forfattere av denne artikkelen] (2014). Changes in Cognitive Function during Psychogeriatric Treatment in Relation to Benzodiazepine Cessation. Pharmacopsychiatry. ISSN 0176-3679. 47(4-5), s. 145–150. doi: 10.1055/s-0034-1381982. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Fjeld, Bente; Burns, Margrete Larsen; Strand, Dag Helge & Vindenes, Vigdis (2014). Long-term stability of morphine, codeine, and 6-acetylmorphine in real-life whole blood samples, stored at -20°C. Forensic Science International. ISSN 0379-0738. 239, s. 6–10. doi: 10.1016/j.forsciint.2014.03.008. Fulltekst i vitenarkiv
• Thaulow, Cecilie Hasselø; Høiseth, Gudrun; Andersen, Jannike Mørch; Handal, Marte & Mørland, Jørg (2014). Pharmacokinetic interactions between ethanol and heroin: a study on post-mortem cases. Forensic Science International. ISSN 0379-0738. 242, s. 127–134. doi: 10.1016/j.forsciint.2014.06.032. Fulltekst i vitenarkiv
• Tveito, Marit; Bramness, Jørgen Gustav; Engedal, Knut; Lorentzen, Bernhard; Refsum, Helge & Høiseth, Gudrun (2014). Psychotropic medication in geriatric psychiatric patients: Use and unreported use in relation to serum concentrations. European Journal of Clinical Pharmacology. ISSN 0031-6970. 70(9), s. 1139–1345. doi: 10.1007/s00228-014-1720-z. Fulltekst i vitenarkiv
• Bogstrand, Stig Tore; Høiseth, Gudrun; Rossow, Ingeborg; Normann, Per Trygve & Ekeberg, Øivind (2014). Prevalence of ethyl glucuronide and ethyl sulphate among patients injured when driving or at work. Alcohol and Alcoholism. ISSN 0735-0414. 50(1), s. 68–73. doi: 10.1093/alcalc/agu070. Fulltekst i vitenarkiv Vis sammendrag

  Presence of EtG or EtS among patients injured when driving or at work may indicate that very low BAC or residual effects of alcohol at the time of the accident may be associated with increased accident risk. The aim of this study was to assess: whether the alcohol metabolites EtG and EtS were present in a sample of patients injured when driving or injured at work, even if their blood alcohol concentration was negative; and, if EtG and EtS were present, what characterized these patients. Methods: Blood samples from patients admitted for treatment of injuries at a Norwegian emergency department were tested for alcohol, EtG and EtS. All samples were also analysed for medicinal and illicit psychoactive substances. Results: One hundred and ninety-two injured patients who were admitted <12 h after injury were included in the study. EtG or EtS were the most prevalent substances in the sample (17%), and a substantial proportion of the patients who tested negative for all other substances tested positive for EtG or EtS (8%). These patients were older than the rest of the sample and drank alcohol more often, according to their self-report. Conclusion: EtG and EtS were prevalent among patients injured when driving or injured at work, including patients negative for all other substances. EtG and EtS should be included in future case–control studies of psychoactive substance use among injured patients to investigate the possible association between residual alcohol effects and injuries.

• Høiseth, Gudrun; Bakke, Eirin; Bachs, Liliana Casulleras & Bramness, Jørgen Gustav (2014). Interaksjoner ved legemiddelassistert rehabilitering. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. 122(10), s. 48–51. Fulltekst i vitenarkiv
• Krabseth, Hege-Merete; Mørland, Jørg & Høiseth, Gudrun (2014). Assistance of ethyl glucuronide and ethyl sulfate in the interpretation of postmortem ethanol findings. International journal of legal medicine (Print). ISSN 0937-9827. 128(5), s. 765–770. doi: 10.1007/s00414-014-1031-z. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Andås, Hilde Teigen; Bachs, Liliana Casulleras & Mørland, Jørg (2014). Impairment due to amphetamines and benzodiazepines, alone and in combination. Drug and Alcohol Dependence. ISSN 0376-8716. 145, s. 174–179. doi: 10.1016/j.drugalcdep.2014.10.013. Fulltekst i vitenarkiv
• Jansen, Mona Dverdal; Knudsen, Gun Peggy; Myhre, Ronny; Høiseth, Gudrun; Mørland, Jørg & Næss, Øyvind [Vis alle 8 forfattere av denne artikkelen] (2014). Genetic variants in loci 1p13 and 9p21 and fatal coronary heart disease in a Norwegian case-cohort study. Molecular Biology Reports. ISSN 0301-4851. 41(5), s. 2733–2743. doi: 10.1007/s11033-014-3096-7. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Tanum, Lars; Tveito, Marit; Kristiansen, Kari Midtbø; Kvande, Kristin & Lorentzen, Bernhard [Vis alle 8 forfattere av denne artikkelen] (2013). A Clinical Study of the Cognitive Effects of Benzodiazepines in Psychogeriatric Patients. Pharmacopsychiatry. ISSN 0176-3679. 46(6), s. 209–213. doi: 10.1055/s-0033-1349131. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Kristiansen, Kari Midtbø; Kvande, Kristin; Lorentzen, Bernhard; Tanum, Lars & Refsum, Helge (2013). Benzodiazepines in Geriatric Psychiatry - What Doctors Report and What Patients Actually Use. Drugs & Aging. ISSN 1170-229X. 30(2), s. 113–118. doi: 10.1007/s40266-012-0045-9. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Morini, Luca; Ganss, Rudiger; Nordal, Kristin & Mørland, Jørg (2013). Higher Levels of Hair Ethyl Glucuronide in Patients with Decreased Kidney Function. Alcoholism: Clinical and Experimental Research. ISSN 0145-6008. 37, s. E14–E16. doi: 10.1111/j.1530-0277.2012.01882.x. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Andersen, Jannike Mørch & Mørland, Jørg (2013). Less glucuronidation of morphine in the presence of ethanol in vivo. European Journal of Clinical Pharmacology. ISSN 0031-6970. 69(9), s. 1683–1687. doi: 10.1007/s00228-013-1533-5. Fulltekst i vitenarkiv
• Graff-Iversen, Sidsel; Jansen, Mona Dverdal; Hoff, Dominic Anthony; Høiseth, Gudrun; Knudsen, Gun Peggy & Magnus, Per [Vis alle 10 forfattere av denne artikkelen] (2013). Divergent associations of drinking frequency and binge consumption of alcohol with mortality within the same cohort. Journal of Epidemiology and Community Health. ISSN 0143-005X. 67(4), s. 350–357. doi: 10.1136/jech-2012-201564. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Magnus, Per; Knudsen, Gun Peggy; Jansen, Mona Dverdal; Næss, Øyvind & Tambs, Kristian [Vis alle 7 forfattere av denne artikkelen] (2013). Is ADH1C genotype relevant for the cardioprotective effect of alcohol? Alcohol. ISSN 0741-8329. 47(2), s. 81–84. doi: 10.1016/j.alcohol.2012.12.005. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Umair, Majid; Mørland, Jørg; Bramness, Jørgen Gustav & Molden, Espen (2012). CYP2C19 genetics in fatal carisoprodol intoxications. European Journal of Clinical Pharmacology. ISSN 0031-6970. 68(11), s. 1561–1565. doi: 10.1007/s00228-012-1278-6. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Nordal, Kristin; Pettersen, Eirik & Mørland, Jørg (2012). Prolonged Urinary Detection Times of EtG and EtS in Patients with Decreased Renal Function. Alcoholism: Clinical and Experimental Research. ISSN 0145-6008. 36(7), s. 1148–1151. doi: 10.1111/j.1530-0277.2011.01713.x. Fulltekst i vitenarkiv
• Høiseth, Gudrun & Bentsen, Håvard (2012). Bruk av antipsykotiske depotinjeksjoner. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 132, s. 301–303. doi: 10.4045/tidsskr.11.0721. Fulltekst i vitenarkiv Vis sammendrag

  Etterlevelse er et stort problem ved bruk av antipsykotiske legemidler. Derfor ble det i 1960-årene utviklet depotinjeksjoner. Ved å redusere vannløseligheten betydelig har man oppnådd at virkestoffet diffunderer langsomt ut fra innstikksstedet, dermed er terapeutisk serumkonsentrasjon sikret igjennom hele perioden. Nyere studier viser at slik behandling kan gi redusert risiko for sykehusinnleggelser og tilbakefall av psykoser, sammenliknet med bruk av tabletter.

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• Mørland, Jørg Gustav; Bachs, Liliana Casulleras & Høiseth, Gudrun (2025). Blackout – alkoholfremkalt hukommelsestap og seksuelle overgrep. 145, s. 1–6. doi: 10.4045/tidsskr.25.0691. Fulltekst i vitenarkiv
• Strand, Maren; Gjerde, Hallvard & Høiseth, Gudrun (2022). Nystagmus among suspected amphetamine impaired drivers. Fulltekst i vitenarkiv
• Musshoff, Frank; Böttcher, Michael; Graw, Matthias; Skopp, Gisela; Neumann, Jasna & Høiseth, Gudrun [Vis alle 7 forfattere av denne artikkelen] (2022). Comment on the upper cutoff level for the alcohol biomarker phosphatidylethanol (PEth) for the assessment of alcohol consumption in forensic practice. Drug Testing and Analysis. ISSN 1942-7603. doi: 10.1002/dta.3432. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Vindenes, Vigdis; Hilberg, Thor & Bogstrand, Stig Tore (2022). Høyt nivå av ferritin og HDL-kolesterol er assosiert med høyt alkoholforbruk. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(17), s. 1–3. doi: 10.4045/tidsskr.22.0431. Fulltekst i vitenarkiv
• Nygaard, Egil; Andersen, Jannike Mørch & Høiseth, Gudrun (2019). Long-term outcomes after prenatal exposure to methadone or buprenorphine: A meta-analysis. Fulltekst i vitenarkiv
• Tveito, Marit; Correll, Christoph U.; Bramness, Jørgen Gustav; Engedal, Knut; Lorentzen, Bernhard & Refsum, Helge [Vis alle 7 forfattere av denne artikkelen] (2015). Correlates of major medication side effects interfering with daily performance: results from a cross-sectional cohort study of older psychiatric patients. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Middelkoop, Gerrit; Mørland, Jørg & Gjerde, Hallvard (2015). Has previous abuse of flunitrazepam been replaced by clonazepam? Fulltekst i vitenarkiv
• Tveito, Marit; Bramnes, Jørgen; Engedal, Knut; Lorentzen, Bernhard; Refsum, Helge & Høiseth, Gudrun (2014). Psykotrope legemidler hos alderspsykiatriske pasienter: etterlevelse og urapportert bruk i relasjon til serumanalyser. Fulltekst i vitenarkiv
• Høiseth, Gudrun; Nordal, Kristin & Mørland, Jørg (2011). PROLONGED URINARY DETECTION TIMES OF ETG AND ETS IN PATIENTS WITH DECREASED RENAL FUNCTION. Alcohol and Alcoholism. ISSN 0735-0414. 46, s. 33–33. Fulltekst i vitenarkiv

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