Document Detail

Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state.
MedLine Citation:
PMID:  23344581     Owner:  NLM     Status:  MEDLINE    
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.
Neal L Benowitz; Andy Z X Zhu; Rachel F Tyndale; Delia Dempsey; Peyton Jacob
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  23     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-07-05     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  135-41     Citation Subset:  IM    
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MeSH Terms
Aryl Hydrocarbon Hydroxylases / genetics*
Base Sequence
Bupropion / blood*,  urine*
DNA Primers
Dopamine Uptake Inhibitors / blood*,  urine*
Genetic Variation*
Oxidoreductases, N-Demethylating / genetics*
Polymerase Chain Reaction
Grant Support
CA 78603/CA/NCI NIH HHS; DA 12393/DA/NIDA NIH HHS; DA U01 020830/DA/NIDA NIH HHS; MOP#86471//Canadian Institutes of Health Research; NCRR UCSF CTSI UL1 RR 024131//PHS HHS; P30 DA012393/DA/NIDA NIH HHS; TMH-10978//Canadian Institutes of Health Research; U01 DA020830/DA/NIDA NIH HHS
Reg. No./Substance:
0/DNA Primers; 0/Dopamine Uptake Inhibitors; 01ZG3TPX31/Bupropion; EC 1.14.13.-/cytochrome P-450 CYP2B6; EC Hydrocarbon Hydroxylases; EC 1.5.-/Oxidoreductases, N-Demethylating

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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