Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Sara Eyal, Hebrew University, Jerusalem, Israel
- Second opponent: Professor Olav Spigset, Department of Clinical Pharmacology, St. Olav Hospital, and Faculty of Medicine and Health Science, The Norwegian University of Science and Technology - NTNU
- Third member and chair of the evaluation committee: Professor Lars Nilsson, Faculty of Medicine, University of Oslo
Chair of the Defence
Pro-Dean for research Jens Petter Berg, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor Cecilie Johannessen Landmark, Faculty of Health Sciences, Oslo Metropolitan University
Summary
About 1/3 of patients with epilepsy continue to experience seizures despite treatment with antiepileptic drugs. Variability in drug concentrations after intake of a given dose, so-called pharmacokinetic variability, contributes to differences in response. Therapeutic drug monitoring by measurement of serum concentrations combined with clinical interpretation of the results can be used to adjust for such variability, and is a tool to individualize and optimize treatment.
The thesis aimed to contribute to improved characterization of pharmacokinetic variability, clinical use and therapeutic drug monitoring of antiepileptic drugs in patients or situations where pharmacological treatment is challenging. The studies examined clobazam in patients with difficult-to-treat epilepsies, lacosamide in children and adolescents, valproate in women of childbearing age and gabapentin which is often used in the elderly and in non-epilepsy indications. Results from routine serum concentration measurements were combined with clinical information to describe how these concentrations were affected by age, gender, the use of other drugs and/or pharmacogenetics. Extensive pharmacokinetic variability was demonstrated for all four drugs, indicating that therapeutic drug monitoring is a better measure of exposure than the dose. Furthermore, including serum concentrations in future research will provide more comprehensive insight when examining efficacy and tolerability of antiepileptic drugs.
Additional information
Contact the research support staff.