Effects of CYP2C9*3 and *13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects

다국어 초록 (Multilingual Abstract)

Glipizide is a second-generation sulfonylureaantidiabetic drug. It is principally metabolized to inactivemetabolites by genetically polymorphic CYP2C9 enzyme.
In this study, we investigated the eff ects of CYP2C9*3 and*13 variant alleles on the pharmacokinetics and pharmacodynamicsof glipizide. Twenty-four healthy Korean volunteers(11 subjects with CYP2C9*1/*1 , 8 subjects withCYP2C9*1/*3 , and 5 subjects with CYP2C9*1/*13 ) wererecruited for this study. They were administered a singleoral dose of glipizide 5 mg. The plasma concentration ofglipizide was quantifi ed for pharmacokinetic analysis andplasma glucose and insulin concentrations were measured aspharmacodynamic parameters. The results represented thatCYP2C9*3 and *13 alleles signifi cantly aff ected the pharmacokineticsof glipizide. In subjects with CYP2C9*1/*3and CYP2C9*1/*13 genotypes, the mean AUC 0–∞ wereincreased by 44.8% and 58.2%, respectively (both P < 0.001),compared to those of subjects with CYP2C9*1/*1 genotype,while eff ects of glipizide on plasma glucose and insulinlevels were not signifi cantly diff erent between CYP2C9genotype groups. In conclusion, individuals carrying the defective CYP2C9*3 and CYP2C9*13 alleles have markedlyelevated plasma concentrations of glipizide comparedwith CYP2C9*1/*1 wild-type.

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