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Association of CYP2B6 , CYP3A5 , and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects
Author(s) -
Kim KA,
Song WK,
Park JY
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.145
Subject(s) - cyp2c19 , pharmacokinetics , sibutramine , cyp2b6 , pharmacology , metabolite , active metabolite , medicine , pharmacogenetics , cyp3a5 , genotype , cyp3a4 , chemistry , metabolism , cytochrome p450 , obesity , biochemistry , weight loss , gene
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. Clinical Pharmacology & Therapeutics (2009) 86 5, 511–518. doi: 10.1038/clpt.2009.145