The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects
The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects
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DOI：
10.1007/s00228-009-0736-2
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Zhong, Da-Fang
中科院分区：
文献类型：
--
作者：
Tan, Bo;Zhang, Yi-Fan;Zhong, Da-Fang
目的探讨CYP2C9和CYP2C19基因多态性对格列吡嗪药动学和药效学的影响。方法18名健康男性按基因型分为3组：ⅰ组、CYP2C9*1/*1组和CYP2C19广泛代谢物组（EMs）；II组为CYP2C9*1/*1和CYP2C19代谢不良者（PMs）；III组CYP2C9*1/*3和CYP2C19 EMs。单剂量5mg格列吡嗪片后，测定36小时的血浆格列吡嗪浓度。同时测定给药后0 ~ 4 h的血糖和胰岛素水平。结果III组血浆浓度-时间曲线下面积（AUC(0-∞)）比i组高2.0倍，口服清除率低51.1%，1h内空腹胰岛素水平变化（δ AUEC（胰岛素0-1h））比i组高3.8倍，格列吡嗪参数变化趋势与III组相似。结论CYP2C9多态性对格列吡嗪的药代动力学和药效学有显著影响，在临床应用中需予以重视。CYP2C19多态性有影响格列吡嗪疗效的倾向，在一定程度上与CYP2C9多态性相似。
Objective To study the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide.Methods Eighteen healthy male subjects were divided into three groups according to their genotypes: group I, CYP2C9*1/*1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C9*1/*1 and CYP2C19 poor metabolizers (PMs); and group III, CYP2C9*1/*3 and CYP2C19 EMs. After a single dose of a 5-mg glipizide tablet, plasma concentrations of glipizide for a 36-h period were determined. Meanwhile, plasma glucose levels and plasma insulin levels were determined from 0 to 4 h after dosing.Results The area under the plasma concentration-time curve (AUC(0-infinity)) was 2.0-fold higher and the oral clearance was 51.1% lower in group III than in group I. The change in fasting insulin level within 1 h (Delta AUEC(insulin0-1h)) in group III was 3.8-fold higher than that in group I. The glipizide parameters in group II exhibited similar tendencies to those in group III.Conclusions These results suggest that CYP2C9 polymorphism significantly influences the pharmacokinetics and pharmacodynamics of glipizide, which needs to be considered in clinical practice. CYP2C19 polymorphism exhibits a tendency to influence the effects of glipizide, to a certain extent similarly to CYP2C9 polymorphism.