• 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.