Tan B, Zhang YF, Chen XY, Zhao XH, Li GX, Zhong DF
The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects. [JOURNAL ARTICLE]
Eur J Clin Pharmacol 2009 Oct 22.
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 ([Formula: see text]) 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.
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.
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