MSACL 2019 EU Abstract

Impact of Body Mass Index on Cytochrome P450 3A Phenotype in Obese Patients

Birgit M. Wollmann (1), Kristine Hole (1), Espen Molden (1,2)
(1) Center for psychopharmacology, Diakonhjemmet Hospital, Oslo (2) Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo

Warning: Undefined variable $headshot in /var/www/html/view_abstract/view_abstract_in_program.php on line 704

Birgit M. Wollmann (Presenter) Diakonhjemmet Hospital, Oslo, Norway >> POSTER (PDF)

Presenter Bio: My PhD topic is on factors responsible for individual variability in drug effect and side effects. My main focus is on the impact of inflammation on drug metabolizing enzymes, and identification of endogenous biomarkers as potential predictors of an individual’s drug metabolism capacity in order to optimize drug treatment.

Background:
PhD candidate. Center for psychopharmacology. Diakonhjemmet Hospital. 2017-current position
Method specialist. Center for psychopharmacology. Diakonhjemmet Hospital. 2015-current position
M. Sc. Pharmacy. University of Oslo. 2010-2015.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

Background
Cytochrome P450 (CYP) 3A4 is abundantly expressed in human liver and small intestine, and is generally regarded as the most important enzyme in drug metabolism. There is a large interindividual variability in CYP3A phenotype (CYP3A4 and CYP3A5) and high body mass index (BMI) is associated with low CYP3A4 expression in both the liver and the small intestine. The aim of this study was to characterize and compare CYP3A phenotype, measured as cholesterol-adjusted plasma levels of 4β-hydroxycholesterol (4βOHC), over time in obese patients initiating a low and very low calorie diet.
Material and methods
Plasma samples from 40 obese patients initiating a 9-week low and very low calorie diet were included in the study. 4βOHC was measured by ultra-performance liquid chromatography-tandem mass spectrometry in samples collected at baseline and after 1, 2, 4, 12 and 24 months. Cholesterol levels and BMI were retrieved from the study database. Wilcoxon signed rank tests were used to compare paired 4βOHC to cholesterol ratios (4βOHC/C) between the different time points.
Results
The median BMI at baseline was 40.3 kg/m2 (range 34.9-58.1 kg/m2). Baseline 4βOHC/C ranged >5-fold (1.8-9.5), with a median value of 4.9, and was significantly lower compared to the medians at the five follow-up time points (median 5.6, 6.7, 7.2, 7.3 and 6.5 after 1, 2, 4, 12 and 24 months, respectively, P<0.01). Median 4βOHC/C after 1 month was also significantly lower compared to the medians at the follow-up time points (P<0.02), except for after 24 months (P>0.4). There were no significant changes in 4βOHC/C between the four last time points (P>0.3). The observed changes in 4βOHC/C were inversely related to changes in BMI.
Conclusions
CYP3A activity increased in obese patients after initiation of a low and very low calorie diet, and the changes were inversely related to the corresponding changes in BMI. Clinically, this may be of importance for obese patients initiating BMI-changing interventions during treatment with CYP3A-metabolised drugs.