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Pharmacogenet Genomics. 2013 Mar;23(3):135-41. doi: 10.1097/FPC.0b013e32835d9ab0.

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

Author information

1
Department of Medicine, Bioengineering and Therapeutic Sciences, Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, California 94143-1220, USA. nbenowitz@medsfgh.ucsf.edu

Abstract

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.

PMID:
23344581
PMCID:
PMC3763712
DOI:
10.1097/FPC.0b013e32835d9ab0
[Indexed for MEDLINE]
Free PMC Article

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