The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects

Abstract

To study the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide. 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. 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 (DeltaAUEC(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. 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.