Document Detail

CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion.
MedLine Citation:
PMID:  23149928     Owner:  NLM     Status:  MEDLINE    
Bupropion is indicated to promote smoking cessation. Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite, hydroxybupropion. We measured plasma bupropion and its metabolite levels in a double-blind, placebo controlled, randomized smoking-cessation trial. Among the treatment-adherent individuals, higher hydroxybupropion concentrations (per μg/ml) resulted in better smoking-cessation outcomes (week 3, 7, and 26 odds ratio (OR) = 2.82, 2.96, and 2.37, respectively, P = 0.005-0.040); this was not observed with bupropion levels (OR = 1.00-1.03, P = 0.59-0.90). Genetic variation in CYP2B6, the enzyme that metabolizes bupropion to hydroxybupropion, was identified as a significant source of variability in hydroxybupropion formation. Our data indicate that hydroxybupropion contributes to the pharmacologic effects of bupropion for smoking cessation, and that variability in response to bupropion treatment is related to variability in CYP2B6-mediated hydroxybupropion formation. These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 μg/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion's cessation outcomes.
A Z X Zhu; L S Cox; N Nollen; B Faseru; K S Okuyemi; J S Ahluwalia; N L Benowitz; R F Tyndale
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  92     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-01-16     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  771-7     Citation Subset:  AIM; IM    
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MeSH Terms
African Americans
Antidepressive Agents, Second-Generation / metabolism*,  therapeutic use*
Aryl Hydrocarbon Hydroxylases / metabolism*
Bupropion / analogs & derivatives,  metabolism*,  therapeutic use*
Double-Blind Method
Logistic Models
Odds Ratio
Oxidoreductases, N-Demethylating / metabolism*
Predictive Value of Tests
Smoking / drug therapy*
Smoking Cessation*
Treatment Outcome
Grant Support
1HLR01081522//PHS HHS; 1P60MD003422/MD/NIMHD NIH HHS; 1U54CA153603/CA/NCI NIH HHS; 86471-1//Canadian Institutes of Health Research; CA091912/CA/NCI NIH HHS; DA012353/DA/NIDA NIH HHS; DA020830/DA/NIDA NIH HHS; MOP86471//Canadian Institutes of Health Research; R01 CA091912/CA/NCI NIH HHS; U01 DA020830/DA/NIDA NIH HHS
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 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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