Document Detail


CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion.
MedLine Citation:
PMID:  23149928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A Z X Zhu; L S Cox; N Nollen; B Faseru; K S Okuyemi; J S Ahluwalia; N L Benowitz; R F Tyndale
Related Documents :
9600478 - Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal...
12494408 - Direct adsorption of low-density lipoprotein and lipoprotein(a) from whole blood: resul...
9051198 - Inhibition of cholesterol ester transfer protein cgs 25159 and changes in lipoproteins ...
16775668 - Effects of withdrawal of xuezhikang, an extract of cholestin, on lipid profile and c-re...
39528 - Cardiovascular profile of 2-(3,4-diethyoxy-beta-methoxyphenethyl) imino-1-methylpyrroli...
20651618 - The soybean concentrated extract proliferates the vagina of adult rats.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
African Americans
Antidepressive Agents, Second-Generation / metabolism*,  therapeutic use*
Aryl Hydrocarbon Hydroxylases / metabolism*
Bupropion / analogs & derivatives,  metabolism*,  therapeutic use*
Double-Blind Method
Humans
Kinetics
Logistic Models
Odds Ratio
Oxidoreductases, N-Demethylating / metabolism*
Predictive Value of Tests
Smoking / drug therapy*
Smoking Cessation*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
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
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 01ZG3TPX31/Bupropion; EC 1.14.13.-/cytochrome P-450 CYP2B6; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.5.-/Oxidoreductases, N-Demethylating
Comments/Corrections

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


Previous Document:  Longitudinal Cystic Fibrosis Care.
Next Document:  Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, ...