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Effect of CYP2B6 genotype on the pharmacokinetics of sibutramine and active metabolites in healthy subjects

Authors
 Jae Yong Chung ; Seong Bok Jang ; Kyungsoo Park ; Min Soo Park ; Yoon Jung Lee 
Citation
 Journal of Clinical Pharmacology, Vol.51(1) : 53~59, 2011 
Journal Title
 Journal of Clinical Pharmacology 
ISSN
 0091-2700 
Issue Date
2011
Abstract
Sibutramine is a pharmacologic intervention for the treatment of obesity. The effect of CYP2B6 genotypes on the pharmacokinetics of sibutramine and its active metabolites (desmethylsibutramine [M1] and didesmethylsibutramine [M2]) was evaluated in 57 healthy subjects. Each subject received a single oral dose of 10 or 15 mg sibutramine, and blood samples were collected up to 72 hours after dosing. The relationship between the genotypes and the pharmacokinetics of sibutramine, M1, and M2 was examined. A statistically significant difference in the elimination half-life (t(1/2)) of sibutramine M1 was found among the 3 genotype groups (P = .0006), between the *1/*1 and *1/*6 groups (P = .0001), and between the *1/*4 and *1/*6 groups (P = .012). The mean value of M1 t(1/2) in *1/*6 (33.3 ± 10.5 hours) was about 58% and 61% greater than that of the *1/*1 group (21.0 ± 7.4 hours) and the *1/*4 group (20.7 ± 9.8 hours), respectively. No significant differences in area under the concentration-time curve or maximum plasma drug concentration were observed between the groups. The CYP2B6*6 allele may be associated with a lower metabolic clearance of the M1 metabolite of sibutramine in human subjects.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/92612
DOI
10.1177/0091270010362906
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pediatrics
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
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Link
 http://onlinelibrary.wiley.com/doi/10.1177/0091270010362906/abstract
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