alexa Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes.


Clinical & Medical Biochemistry

Author(s): Niemi M, Cascorbi I, Timm R, Kroemer HK, Neuvonen PJ,

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Abstract OBJECTIVES: Our objective was to investigate the effects of genetic polymorphisms of cytochrome P450 (CYP) 2C9 on the pharmacokinetics of glyburide (INN, glibenclamide) and glimepiride, two widely used sulfonylurea antidiabetic drugs. METHODS: We conducted CYP2C9 genotyping for 29 healthy volunteers who had participated in our previous pharmacokinetic studies on glyburide or glimepiride. RESULTS: There were 17 subjects (59\%) with the CYP2C9*1/*1 (wild-type) genotype, 8 (28\%) with the CYP2C9*1/*2 genotype, 3 (10\%) with the CYP2C9*1/*3 genotype, and 1 (3\%) with the CYP2C9*2/*3 genotype. The pharmacokinetics of glyburide or glimepiride were not significantly changed among subjects with the CYP2C9*1/*2 genotype. However, in individuals heterozygous for the CYP2C9*3 allele, the median total area under the plasma concentration-time curve of glyburide (n = 2) was 280\% (P < or = .05) and that of glimepiride (n = 3) was 267\% (P < or = .01) of the respective values in subjects with the CYP2C9*1/*1 genotype (n = 5 and n = 12, respectively). Blood glucose responses to glyburide and glimepiride were not significantly affected by the CYP2C9 genotype. CONCLUSIONS: Genetic polymorphisms of CYP2C9 markedly affect the pharmacokinetics of both glyburide and glimepiride. The influence of the CYP2C9*3 variant allele on glyburide and glimepiride pharmacokinetics may be clinically significant. This article was published in Clin Pharmacol Ther and referenced in Clinical & Medical Biochemistry

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