Publications
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Rognstad, Stine; Søraas, Camilla Lund; Brunborg, Cathrine; Halvorsen, Lene Vernås; Brobak, Karl Marius & Olsen, Eirik
[Show all 15 contributors for this article]
(2025).
Pharmacokinetic Variability of Amlodipine Serum Concentration and Effect on Blood Pressure in Patients Treated for Hypertension.
Pharmacology Research & Perspectives.
13(4).
doi:
10.1002/prp2.70140.
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We investigated the effects of age, sex, BMI, total number of prescribed daily pills, common biomarkers, and CYP3A4/5 polymorphisms on dose‐adjusted amlodipine concentration (CDR) in hypertensive patients. We also examined associations between the same covariates, dose, and serum amlodipine concentrations with uncontrolled hypertension. Amlodipine concentrations were measured in 471 patients treated with ≥ 2 antihypertensive drugs, with 50% having uncontrolled hypertension (daytime ambulatory blood pressure ≥ 135 mmHg). CYP analyses were performed in a subgroup of 258 patients, 82% of these uncontrolled. Women used lower daily doses ( p < 0.001) and had higher CDR ( p < 0.001) than men. CDR increased with age ( p < 0.001), reduced kidney function ( p < 0.001) and CYP3A4*22 allele ( p = 0.006). Patients with uncontrolled hypertension had lower CDR ( p = 0.014). Women were half as likely as men to have uncontrolled hypertension ( p = 0.002). At the group level, a 20 nmol/L increase in concentration, corresponding to adjustment from 5 to 10 mg, was associated with a 16.5% decreased probability of uncontrolled hypertension. Female sex, increasing age, reduced kidney function, and reduced CYP3A4 activity increased amlodipine CDR. The included covariates explained 41% of the amlodipine concentration variability. Females had a reduced probability of uncontrolled hypertension, and increased amlodipine concentration was associated with decreased probability of uncontrolled hypertension. We suggest using TDM of amlodipine as an aid for clinical decision‐making in cases of unsatisfactory treatment response, to identify possible non‐adherence or pharmacokinetic deviations. Trial Registration: ClinicalTrials.gov identifier: NCT03209154
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Bratberg, Aase; Nygaard, Ilah Le; Løhne, Kari; Gustavsen, Ingebjørg & Opdal, Mimi Stokke
(2025).
Serum Ethanol Concentrations in Relation to Sex and Age in Patients Admitted to a Large Emergency Department During 2015–2020.
Basic & Clinical Pharmacology & Toxicology.
ISSN 1742-7835.
136(1).
doi:
10.1111/bcpt.14118.
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We examined the number of patients tested for serum ethanol concentration (SEC) at admission to a large Emergency Department (ED) and the relationship of SEC with sex and age. SEC was analysed by enzymatic method. We retrieved SEC in patient samples from the ED during 2015–2020 from the laboratory information system. Altogether, 174 378 patients were admitted, and 7.3% were tested for SEC. Of these, 35.3% had a positive test. The percentage of patients tested increased from 4.8% in 2015 to 14.4% in 2020. A total of 416 patients had more than one positive SEC. For individual data, we included the first positive test per patient, n = 3607. Of these, 73% were men and 27% were women. The median SEC for both men and women was 1.9 g/L. About 4.4% had a SEC ≥ 3.5 g/L. The median SEC in patients aged 30–59 years was 0.2 g/L higher than the 12–29 and ≥ 60 age groups. In conclusion, the increase in the percentage of patients tested did not lead to a corresponding increase in ethanol-positive tests. There was a large predominance of men, the median SEC was the same for men and women and highest in the 30–59 age group.
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Halvorsen, Lene Vernås; Søraas, Camilla Lund; Larstorp, Anne Cecilie Kjeldsen; Hjørnholm, Ulla; Kjær, Vibeke Norheim & Liestøl, Knut
[Show all 21 contributors for this article]
(2024).
Effect of Therapeutic Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.
American Journal of Hypertension.
ISSN 0895-7061.
37(10),
p. 826–836.
doi:
10.1093/ajh/hpae059.
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BACKGROUND Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT). METHODS Patients were ≥18 years on stable treatment with at least 2 antihypertensive agents. We planned to randomize 80 nonadherent patients with a systolic daytime ambulatory BP ≥135 mm Hg to TDM intervention or not. The control group and the study personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on the disease process and the importance of BP treatment were given to both groups. RESULTS From 2017 to 2022, we randomized 46 diagnosed nonadherent from a total of 606 patients with uncontrolled HT. The TDM group had a 6.7 (±14.5) mm Hg reduction from 147.9 (±10.3) to 141.1 (±14.1) mm Hg, and the control group experienced a 7.3 (±13.2) mm Hg reduction from 147.1 (±9.2) to 139.1 (±17.4) mm Hg, P = 0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at 3 months, P = 0.51. CONCLUSIONS In our prospective multicenter clinical trial of uncontrolled and nonadherent hypertensive patients, we found no additional effect of TDM on BP and drug adherence compared with standard care.
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Havig, Stine Marie; Berg-Pedersen, Riikka Mari; Krabseth, Hege-Merete; Muller, Lill Dannevig; Haugaa, Kristina Ingrid Helena Hermann & Zare, Hasse Khiabani
[Show all 9 contributors for this article]
(2024).
Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients.
Basic & Clinical Pharmacology & Toxicology.
ISSN 1742-7835.
134,
p. 519–530.
doi:
10.1111/bcpt.13982.
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Methadone (R,S-methadone) can prolong the QT interval. R-methadone inhibits cardiac potassium channel function less than S-methadone. We tested if switching from methadone to R-methadone would reduce corrected QT (QTc) intervals in methadone maintenance treatment (MMT) patients. Nine patients, with automatically read QTc intervals ≥450 ms, were required to detect a 20 ms (clinically relevant) reduction in QTc intervals with 15 ms standard deviation (SD) and 90% power. Nine stabilized MMT patients, using median (range) 70 (40–120) mg methadone, were included. Data (ECG recordings, serum samples, and withdrawal symptoms) were collected both before drug intake (Cmin) and at 3 h after drug intake (Cmax), and were collected on the day before the switch from methadone to equipotent R-methadone dose and at 14 and 28 days after the switch. A cardiologist calculated QTc intervals retrospectively. Serum electrolytes and methadone concentrations were measured. Mean QTc intervals at Cmin were 472 ms and 422 ms on methadone (automatically and manually read) and 414 ms on R-methadone (manually read). Mean (SD) change in QTc intervals was −8 (10) ms (p = 0.047) at Cmin but non-significant at Cmax. R-methadone showed a concentration-dependent relationship with QTc intervals. Switching to R-methadone reduced QTc intervals, but far less than the 20 ms considered clinically relevant.
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Thorstensen, Christian; Clasen, Per-Erik; Rognstad, Stine; Haldsrud, Renate; Føreid, Siri & Helstrøm, Trine
[Show all 16 contributors for this article]
(2022).
Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension.
Journal of Pharmaceutical and Biomedical Analysis.
ISSN 0731-7085.
219.
doi:
10.1016/j.jpba.2022.114908.
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We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs.
For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were acceptable. The accuracy of the internal controls was in the range 85–121 %, and the intermediate precision for all drugs was 4–28 %.
The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5–10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the recommended maximum daily dose. We report the maximum (Cmax) and minimum (Cmin) drug concentrations after drug intake. The inter-individual pharmacokinetic variability at Cmin was 18-fold for hydrochlorothiazide, 22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan.
Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control.
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Halvorsen, Lene Vernås; Bergland, Ola Undrum; Søraas, Camilla Lund; Larstorp, Anne Cecilie Kjeldsen; Hjørnholm, Ulla & Kjær, Vibeke Norheim
[Show all 14 contributors for this article]
(2022).
Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy.
Journal of the American Heart Association (JAHA).
11(18).
doi:
10.1161/JAHA.121.025879.
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Background
Measurement of serum concentrations of drugs is a novelty found useful in detecting poor drug adherence in patients taking ≥2 antihypertensive agents. Regarding patients with treatment‐resistant hypertension, we previously based our assessment on directly observed therapy. The present study aimed to investigate whether serum drug measurements in patients with resistant hypertension offer additional information regarding drug adherence, beyond that of initial assessment with directly observed therapy.
Methods and Results
Nineteen patients assumed to have true treatment‐resistant hypertension and adherence to antihypertensive drugs based on directly observed therapy were investigated repeatedly through 7 years. Serum concentrations of antihypertensive drugs were measured by ultra‐high‐performance liquid chromatography–tandem mass spectrometry from blood samples taken at baseline, 6‐month, 3‐year, and 7‐year visits. Cytochrome P450 polymorphisms, self‐reported adherence and beliefs about medicine were performed as supplement investigations. Seven patients (37%) were redefined as nonadherent based on their serum concentrations during follow‐up. All patients reported high adherence to medications. Nonadherent patients expressed lower necessity and higher concerns regarding intake of antihypertensive medication (P=0.003). Cytochrome P450 polymorphisms affecting metabolism of antihypertensive drugs were found in 16 patients (84%), 21% were poor metabolizers, and none were ultra‐rapid metabolizers. Six of 7 patients redefined as nonadherent had cytochrome P450 polymorphisms, however, not explaining the low serum drug concentrations measured in these patients.
Conclusions
Our data suggest that repeated measurements of serum concentrations of antihypertensive drugs revealed nonadherence in one‐third of patients previously evaluated as adherent and treatment resistant by directly observed therapy, thereby improving the accuracy of adherence evaluation.
Registration
URL: https://www.clinicaltrials.gov; unique identifier: NCT01673516.
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Bergland, Ola Undrum; Halvorsen, Lene Vernås; Søraas, Camilla Lund; Hjørnholm, Ulla; Kjær, Vibeke Norheim & Rognstad, Stine
[Show all 22 contributors for this article]
(2021).
Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations.
Hypertension.
ISSN 0194-911X.
78(3),
p. 617–628.
doi:
10.1161/HYPERTENSIONAHA.121.17514.
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Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment.
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Rognstad, Stine; Søraas, Camilla Lund; Bergland, Ola Undrum; Høieggen, Aud; Strømmen, Magnus & Helland, Arne
[Show all 7 contributors for this article]
(2020).
Establishing Serum Reference Ranges for Antihypertensive Drugs.
Therapeutic Drug Monitoring.
ISSN 0163-4356.
43(1),
p. 116–125.
doi:
10.1097/FTD.0000000000000806.
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Background: Therapeutic drug monitoring (TDM) involves the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50% of hypertensive patients treated with lifestyle changes and antihypertensive drugs fail to achieve blood pressure control. Serum drug concentration measurements could be useful to select the optimal drugs in adjusted doses and to identify nonadherence. Implementation of TDM in clinical routine for antihypertensive drugs depends on established serum reference ranges. Methods: Commonly used antihypertensive drugs were identified based on prescription data. The authors performed a review of authoritative literature on reported serum drug concentrations and calculated expected concentrations from previously reported pharmacokinetic parameters with commonly prescribed daily doses. Finally, serum drug concentrations in samples from patients undergoing antihypertensive treatment were measured. Results: Serum reference ranges for 24 frequently used antihypertensive drugs were established based on results from 3 approaches. Conclusions: Serum drug concentration measurements, interpreted in light of the established reference ranges, together with blood pressure measurements and other clinical data, may help identify nonadherent patients and tailor individual antihypertensive treatment when deviant drug responses appear in line with the concept of personalized medicine.
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Burns, Margrete Larsen; Kinge, Einar; Opdal, Mimi Stokke; Johannessen, Svein Ivar & Landmark, Cecilie Johannessen
(2019).
Therapeutic drug monitoring of gabapentin in various
indications.
Acta Neurologica Scandinavica.
ISSN 0001-6314.
139(5),
p. 446–454.
doi:
10.1111/ane.13075.
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Muller, Lill Dannevig & Opdal, Mimi Stokke
(2018).
Developing a rapid semi-automated sample preparation with alkaline hydrolysis in a 96-well plate for quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine samples by UHPLC-MS/MS.
Journal of Pharmaceutical and Biomedical Analysis.
ISSN 0731-7085.
161,
p. 296–304.
doi:
10.1016/j.jpba.2018.08.045.
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Haga, Christian; Opdal, Mimi Stokke; Tuv, Silja Skogstad; Zahl, Per Henrik & Stenberg-Nilsen, Hanne
(2016).
Legemiddelsikkerhet ved bytte av digitalispreparat i Norge.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
136(20),
p. 1714–1718.
doi:
10.4045/tidsskr.15.0161.
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Burns, Margrete Larsen; Baftiu, Arton; Opdal, Mimi Stokke; Johannessen, Svein Ivar & Landmark, Cecilie Johannessen
(2016).
Therapeutic drug monitoring of clobazam and its metabolite-impact of age and comedication on pharmacokinetic variability.
Therapeutic Drug Monitoring.
ISSN 0163-4356.
38(3),
p. 350–357.
doi:
10.1097/FTD.0000000000000272.
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Kristiansen, Marianne; Piehler, Armin; Grimholt, Runa Marie; Opdal, Mimi Stokke; Foss, Kari Bente & Urdal, Petter
(2014).
Serum bilirubin concentration in healthy adult North-Europeans is strictly controlled by the UGT1A1 TARepeat variants.
PLOS ONE.
9(2).
doi:
10.1371/journal.pone.0090248.
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Al-Samarraie, MSJ; Karinen, Ritva Anneli; Mørland, Jørg & Opdal, Mimi Stokke
(2010).
Blood GHB concentrations and results of medical examinations in 25 car drivers in Norway.
European Journal of Clinical Pharmacology.
ISSN 0031-6970.
66(10),
p. 987–998.
doi:
10.1007/s00228-010-0870-x.
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Øiestad, Elisabeth Leere; Johansen, Unni; Stokke, Opdal Mimi; Bergan, Stein & Christophersen, Asbjørg S.
(2009).
Determination of digoxin and digitoxin in whole blood.
Journal of Analytical Toxicology.
ISSN 0146-4760.
33(7),
p. 372–378.
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Samarrai, Al; Karinen, Ritva Anneli; Rognum, T; Hasvold, Inger; Stokke, Opdal Mimi & Christophersen, Asbjørg S.
(2009).
Lethal Poisoning with Ethiofencarb and Ethanol.
Journal of Analytical Toxicology.
ISSN 0146-4760.
33(7),
p. 389–392.
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Khiabani, Hassan; Stokke, Opdal Mimi & Mørland, Jørg
(2008).
Blood alcohol concentrations in apprehended drivers of cars and boats suspected to be impaired by the police.
Traffic Injury Prevention.
ISSN 1538-9588.
9(1),
p. 31–36.
doi:
10.1080/15389580701737629.
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Al-Samarraie, Muhammad; Khiabani, Hassan & Stokke, Mimi Opdal
(2007).
Khat - et nytt rusmiddel i Norge.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
127(5),
p. 574–576.
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Kristoffersen, Lena; Øiestad, Elisabeth Leere; Opdal, Mimi Stokke; Krogh, Mette; Lundanes, Elsa & Christophersen, Asbjørg S.
(2007).
Simultaneous determination of 6 beta-blockers, 3 calcium-channel antagonists, 4 angiotensin-II antagonists and 1 antiarrhytmic drug in post-mortem whole blood by automated solid phase extraction and liquid chromatography mass spectrometry - Method development and robustness testing by experimental design.
Journal of chromatography. B.
ISSN 1570-0232.
850(1-2),
p. 147–160.
doi:
10.1016/j.jchromb.2006.11.030.
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Bernard, Jean-Paul; Stokke, Mimi Opdal; Karinen, Ritva Anneli; Mørland, Jørg & Khiabani, Hassan
(2007).
Relationship between methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in urine samples from Norwegian prisons.
European Journal of Clinical Pharmacology.
ISSN 0031-6970.
63(8),
p. 777–782.
doi:
10.1007/s00228-007-0314-4.
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Background:
Methadone is a widely used maintenance treatment in rehabilitation of opioid addiction the world over. Methadone is metabolised in the body to a number of inactive metabolites, but primarily to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). The Division of Forensic Toxicology and Drug Abuse (DFTDA), at the Norwegian Institute of Public Health, carries out drug analysis in urine samples from all prisons in Norway. Testing for methadone and EDDP in urine is also carried out, on request. Results are stored in a secure database at the DFTDA.
Objectives:
The aims of the present study were to 1. Observe variation of methadone and EDDP concentrations in urine with urinary pH, in a large material of prison inmate urine samples, and 2. Analyse methadone positive/EDDP negative results, and investigate whether such results could occur naturally and without sample tampering.
Methods:
All urine results positive for methadone over the period 2004-2005 were collected from our result database. The relationship between methadone and EDDP excretion in urine, and urinary pH, was observed for these cases. Cases that were positive for methadone but negative for EDDP were picked out and studied individually.
Results:
1539 urine samples positive for methadone were found in our database for the period 2004-2005. Our results showed a strong correlation between the concentration of methadone in urine and urinary pH, with higher concentrations of methadone present at lower pH levels. Cases that were positive for methadone but negative for EDDP were rare, and amounted to only 5 (0.3% of the case material). These cases are presented in further detail.
Conclusion:
Methadone excretion in urine is dependent on urinary pH. Methadone positive/EDDP negative results may suggest sample tampering in some, but not all, cases.
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Stokke, Mimi; Grønvold, Trude; Siebke, Anne Marie; Skjæggestad, O & Strømme, Johan Henrik
(1998).
Serial measurements of cardiac markers to rule in or out acute myocardial damage less than 3 h after admission in acute chest pain patients without ECG-signs of acute myocardial infarction.
Scandinavian Journal of Clinical and Laboratory Investigation.
ISSN 0036-5513.
58(4),
p. 331–338.
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Stokke, Mimi; Hagelin, Else Marie; Mende, Ulrike & Brørs, Odd
(1996).
Stable guanosine 5'-triphosphate-analogues inhibit specific (+)-[3H]isradipine binding in rat hearts by a Ca(2+)-lowering, G protein-independent mechanism.
Pharmacology and Toxicology.
ISSN 0901-9928.
78(1),
p. 28–36.
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Stokke, Mimi; Kirkebøen, Knut Arvid; Næss, Pål Aksel; Hagelin, Else Marie; Ilebekk, Arnfinn & Brørs, Odd
(1996).
Equal changes in L-type calcium channel density after 60 min of ischaemia in normal and ischaemically preconditioned porcine myocardium.
Acta Physiologica Scandinavica.
ISSN 0001-6772.
157(2),
p. 147–155.
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Stokke, Mimi; Hagelin, Else Marie & Brørs, Odd
(1996).
Effects of ATP on specific [3H](+)-isradipine binding in rat ventricular cardiomyocytes.
European Journal of Pharmacology.
ISSN 0014-2999.
303(1-2),
p. 115–122.
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Stokke, Mimi; Aksnes, Gunnar; Lande, Knut; Hagelin, Else Marie & Brørs, Odd
(1994).
Density of L-type calcium channels in ischaemically preconditioned porcine heart regions.
Acta Physiologica Scandinavica.
ISSN 0001-6772.
150(4),
p. 425–430.
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Stokke, Mimi; Hagelin, Else Marie; Poulsson, Claire; Patel, Renuka; Haile, Y & Brørs, Odd
(1992).
Inhibition by amiloride and quinacrine of specific [3H]nitrendipine binding to rat cardiac membranes.
Journal of Pharmacology and Experimental Therapeutics.
ISSN 0022-3565.
260(3),
p. 1366–1372.
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Stokke, Mimi; Hagelin, Else Marie; Poulsson, Claire & Brørs, Odd
(1992).
Ca2+ modulates the inhibition of (+)-[3H]isradipine binding by amiloride and quinacrine.
European Journal of Pharmacology.
ISSN 0014-2999.
227(4),
p. 379–384.
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Opdal, Mimi Stokke & Krajci, Peter
(2017).
Individual dosing of a methadone maintenance patient with reported opioid withdrawal symptoms.
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Bernard, Jean-Paul; Stokke, Mimi Opdal; Mørland, Jørg & Khiabani, Hassan Zare
(2007).
Methadone related deaths in Norway 2004 - 2006.
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Objective: Methadone, a potent opioid receptor agonist, is the most commonly used drug in the treatment of opioid dependence in Norway. Methadone’s side-effects and toxicity are well documented, and the potential for a rise in the incidence of methadone related deaths due to greater methadone availability is worrying. This study aims to follow the occurrence and pattern of methadone related deaths over a three year period. We will also examine cases where methadone was present at toxicological analysis post-mortem and assess what role methadone toxicity played in the cause of death.
Methods: Toxicological results where methadone was positive were collected from a database of forensic autopsies at the Division of Forensic Toxicology and Drug Abuse (DFTDA). Cases were divided into those where methadone was the only drug present and those where other drugs were present in addition to methadone. All cases were assessed individually.
Results: A total of 176 methadone related deaths were identified from our database of approximately 5400 cases for the period 2004 through 2006. Of these, 143 were male and 33 female. Methadone was the only finding at toxicological analysis in just 6 (3.4%) of these cases. Methadone concentrations in blood varied from 0.06 mg/l to 4.64 mg/l, with a median concentration of 0.43 mg/l. A variety of other substances were also detected in blood, the 3 most common being tetrahydrocannabinol (THC, the primary psychoactive constituent of cannabis), and metabolic products of the benzodiazepines diazepam (N-desmethyldiazepam) and clonazepam (7-aminoclonazepam), respectively. Morphine was detected in 35 cases. The mean number of additional substances detected in these cases was 4.
Conclusion: Methadone related deaths in Norway have risen over the past years. Methadone was most often detected in combination with other substances. These results may suggest that patients using methadone have a significant use of other substances, both illegal and prescription medicines. Alternatively, results may indicate that the majority of those involved in methadone related deaths are not enrolled in rehabilitation programs, and that the source of methadone in these cases is diversion. The study is still ongoing, and further analysis of the results is necessary. We are in the process of coupling our material to the National cause of death register and regional registers of patients enrolled in rehabilitation programs (LAR).
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Bernard, Jean-Paul; Stokke, Mimi Opdal & Khiabani, Hassan
(2006).
Generelle farmakodynamiske prinsipper.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
126(16),
p. 2107–2109.
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Sammendrag:
Farmakodynamikk handler om hvordan ligander (legemidler, rusmidler, giftstoffer og hormoner) virker på sine målorganer i kroppen og utløser effekter (enten ønsket eller uønsket). Interaksjon mellom legemidler og mottakerproteiner er spesifikk og selektiv i organismen. Mottakerproteinene tilhører stort sett til en av fire grupper; enzymer, transportproteiner, ionekanaler og reseptorer.
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Opdal, Mimi Stokke
(2004).
Clinical pharmacology Education and Inturnship.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
124(13-14),
p. 1828–1829.
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Opdal, Mimi Stokke
(1996).
Modulation of cardiac Ca2+ antagonist binding by drugs, nucleotides, divalent cations and ischemia.
Department of Pharmacology, Faculty of Medicine, University of Oslo and Division of Clinical Pharmacology and Toxicology, Clinical Chemistry Department, Ullevål University Hospital [Norwegian Society.
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Published
Sep. 16, 2014 9:25 AM
- Last modified
Apr. 23, 2024 10:45 AM
