| CYP2B6 and Bupropion's Smoking-Cessation Pharmacology: The Role of Hydroxybupropion. | |
| | |
MedLine Citation:
|
PMID: 23149928 Owner: NLM Status: Publisher |
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.Clinical Pharmacology & Therapeutics (2012); advance online publication 14 November 2012. doi:10.1038/clpt.2012.186. |
| | |
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 Date: 2012-11-14 |
Journal Detail:
|
Title: Clinical pharmacology and therapeutics Volume: - ISSN: 1532-6535 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2012 Nov |
Date Detail:
|
Created Date: 2012-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1] Center for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
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, ...