Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Johan Sundström, Uppsala University, Sweden
- Second opponent: Professor Maria Kjellsson, Uppsala University, Sweden
- Third member and chair of the evaluation committee: Associate Professor Kjetil Wessel Andressen, University of Oslo
Chair of the Defence
Professor II Benedicte Paus, University of Oslo
Principal Supervisor
Associate Professor Mimi Stokke Opdal, University of Oslo
Summary
Many patients with hypertension do not achieve adequate blood pressure control despite prescribed antihypertensive medication. This thesis demonstrates that measurement of serum drug concentrations—therapeutic drug monitoring (TDM)—can be a valuable tool to understand why treatment fails in certain individuals.
In the thesis “Application of serum drug measurement for antihypertensive drugs in patients with uncontrolled hypertension – method development and pharmacokinetic variability”, Stine Rognstad and colleagues developed an analytical method (UHPLC–MS/MS) to quantify the most used antihypertensive drugs in Norway. They also established reference ranges for expected serum concentrations for recommended doses based on calculations and serum measurements.
These tools may help clinicians to evaluate whether a patient is receiving an appropriate dose and whether the medication is taken as prescribed.
The study of amlodipine, a widely used calcium channel blocker for treating hypertension, revealed substantial interindividual variability in serum concentrations. Women, older patients, individuals with reduced renal function, and patients with low enzyme activity (CYP3A4/5) were more likely to exhibit elevated amlodipine levels. The overall 10 covariates investigated accounted for 45% of the variability in amlodipine concentrations. Both female sex and higher serum concentrations were associated with improved blood pressure control.
The findings show that TDM can identify issues such as non adherence, incorrect dosing, and atypical drug metabolism — factors that cannot be identified through blood pressure measurement alone.
The overall message from this thesis is that the established serum reference ranges may be used to interpret drug concentrations in relation to blood pressure and other clinical findings, to assess adherence, and to optimize drug dosing. TDM may be a valuable tool to reduce the proportion of patients with uncontrolled hypertension and to individualize hypertension treatment.
Additional information
Contact the research support staff.