Trial lecture - time and place
04.10.2022, 10.15, Auditorium, Gydas vei 8
Effects of age on cytochrome P450-mediated drug metabolism
Conferral summary
Variasjon i farmakokinetiske prosesser kan medføre bivirkninger eller manglende effekt av legemidler, og er en viktig årsak til ulik legemiddelrespons mellom individer. I dette doktorgradsarbeidet ble det undersøkt hvordan fedme, bariatrisk kirurgi og type 2 diabetes påvirker farmakokinetiske prosesser, med fokus på sentrale legemiddelmetaboliserende enzymer. Funnene i avhandlingen kan bidra til å optimalisere legemiddelbehandlingen og dosering i disse pasientene.
Main research findings
The effect of many drugs may be altered in different diseases due to changes in pharmacokinetic processes. In this thesis, we have investigated the impact of type 2 diabetes, obesity, and bariatric surgery on pharmacokinetics, focusing on key drug-metabolizing enzymes. The results show that the activity of specific drug-metabolizing enzymes is downregulated in patients with type 2 diabetes and/or obesity. Thus, dose adjustments may be required for certain drugs to avoid adverse events or therapeutic failure in these patients. Contrary, bariatric surgery seems to have less clinical relevance for drug dosing in the early period after surgery, although it is challenging to extrapolate the results to other drugs than those investigated in this thesis. Additionally, this thesis presents valuable information on two of the metrics (midazolam and 4β-hydroxycholesterol) commonly used to determine individual activity of the most important drug-metabolizing enzyme. Overall, it appears that midazolam does not always reflect the activity of this enzyme and that the endogenous biomarker 4β-hydroxycholesterol may be a valuable supplement in certain studies using midazolam.
Read more (in Norwegian)
Overdriven uro for dosering av legemiddel etter fedmekirurgi (Titan, 4. mai 2022)