Glipizide is a second-generation sulfonylurea antidiabetic drug. It is principally metabolized to inactive metabolites by genetically polymorphic CYP2C9 enzyme. In this study, we investigated the effects of CYP2C9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide. Twenty-four healthy Korean volunteers (11 subjects with CYP2C9*1/*1, 8 subjects with CYP2C9*1/*3, and 5 subjects with CYP2C9*1/*13) were recruited for this study. They were administered a single oral dose of glipizide 5 mg. The plasma concentration of glipizide was quantified for pharmacokinetic analysis and plasma glucose and insulin concentrations were measured as pharmacodynamic parameters. The results represented that CYP2C9*3 and *13 alleles significantly affected the pharmacokinetics of glipizide. In subjects with CYP2C9*1/*3 and CYP2C9*1/*13 genotypes, the mean AUC_0–∞ were increased by 44.8% and 58.2%, respectively (both P < 0.001), compared to those of subjects with CYP2C9*1/*1 genotype, while effects of glipizide on plasma glucose and insulin levels were not significantly different between CYP2C9 genotype groups. In conclusion, individuals carrying the defective CYP2C9*3 and CYP2C9*13 alleles have markedly elevated plasma concentrations of glipizide compared with CYP2C9*1/*1 wild-type.

格列吡嗪是第二代磺脲类抗糖尿病药物。它主要通过遗传多态性 CYP2C9 酶代谢为无活性代谢物。在这项研究中，我们研究了CYP2C9*3和*13变异等位基因对格列吡嗪药代动力学和药效学的影响。24名健康的韩国志愿者（11名CYP2C9*1/*1受试者、8名CYP2C9*1/*3受试者和5名CYP2C9*1/*13受试者) 被招募参加这项研究。他们被给予单次口服剂量的格列吡嗪5 mg。对格列吡嗪的血浆浓度进行量化以进行药代动力学分析，并测量血浆葡萄糖和胰岛素浓度作为药效学参数。结果表明CYP2C9*3和*13等位基因显着影响格列吡嗪的药代动力学。在具有CYP2C9*1/*3和CYP2C9*1/*13基因型的受试者中，与具有CYP2C9*1 的受试者相比，平均 AUC _0–∞分别增加了 44.8% 和 58.2%（均P < 0.001） /*1基因型，而格列吡嗪对血浆葡萄糖和胰岛素水平的影响在CYP2C9基因型组之间没有显着差异。总之，与CYP2C9*1/*1野生型相比，携带有缺陷的CYP2C9*3和CYP2C9*13等位基因的个体具有显着升高的格列吡嗪血浆浓度。