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- Title
Association of CYP2B6, CYP3A5, and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects.
- Authors
Kim, K. A.; Song, W. K.; Park, J. Y.
- Abstract
We assessed the association of CYP2B6, CYP3A5, and CYP2C19 polymorphisms with sibutramine pharmacokinetics. Forty six healthy male subjects were enrolled, and their CYP2B6 (*4 and *6), CYP3A5 (*3), and CYP2C19 (*2, and *3) genotypes were analyzed. After a single 15-mg dose of sibutramine was administered, plasma concentrations of sibutramine and its metabolites, M1 and M2, were measured. CYP2B6 and CYP3A5 polymorphisms did not affect the pharmacokinetics of sibutramine and its metabolites. However, the CYP2C19 genotype substantially influenced plasma levels of sibutramine and its metabolites. The mean area under the curve (AUC) of sibutramine in CYP2C19 intermediate metabolizers (IMs; *1/*2 or *1/*3) and poor metabolizers (PMs; *2/*2, *2/*3)) was 18.5 and 252.2% higher, respectively, than the AUC in extensive metabolizers (EMs, *1/*1) (P < 0.001). The AUC of M1 metabolite in IMs and PMs was 22.5 and 148.0% higher, respectively, than that of EMs (P < 0.001). Our findings indicate that the CYP2C19 genotype substantially affects the pharmacokinetics of sibutramine.
- Subjects
GENETIC polymorphisms; SIBUTRAMINE; PHARMACOKINETICS; METABOLITES; DRUG administration
- Publication
Clinical Pharmacology & Therapeutics, 2009, Vol 86, Issue 5, p511
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2009.145