Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state.

Pharmacogenet Genomics

Department of Medicine, Bioengineering and Therapeutic Sciences, Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, California 94143-1220, USA.

Published: March 2013

Background: Bupropion, an antidepressant and smoking cessation medication, is metabolized to hydroxybupropion (HB), an active metabolite, primarily by CYP2B6.

Objectives: To compare plasma concentrations of bupropion and metabolites at steady state in healthy volunteers with and without CYP2B6 genetic variants.

Methods: In a genotype-guided study of 42 healthy individuals, we measured the plasma and urine concentrations of bupropion and its metabolites, HB, threohydrobupropion, and erythrohydrobupropion after 7 days of sustained-release bupropion dosing.

Results: CYP2B6*6 and *18 gene variants were associated with ~33% reduced concentrations of HB, with no effects on concentrations of bupropion or other metabolites. We could account for 50% of the variation in HB concentrations in a model including genotype and sex.

Conclusion: As HB is active and its steady-state concentrations are more than 10 times higher than bupropion, CYP2B6 variants are likely to affect pharmacological activity. Because of the large individual variation within the genotype group, the use of therapeutic drug monitoring for dose optimization may be necessary.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763712PMC
http://dx.doi.org/10.1097/FPC.0b013e32835d9ab0DOI Listing

Publication Analysis

Top Keywords

concentrations bupropion
16
bupropion metabolites
16
cyp2b6 genetic
8
plasma urine
8
urine concentrations
8
metabolites steady
8
steady state
8
concentrations
7
bupropion
7
influence cyp2b6
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!