Effect of genetic polymorphisms on the pharmacokinetics and efficacy of glimepiride in a Korean population

Abstract

Backgrounds: Glimepiride is a commonly used sulfonylurea hypoglycemic agent. There is considerable interindividual variation in the response to sulfonylurea for patients with type 2 diabetes. The purpose of this study was to investigate whether genetic variations influence the efficacy of glimepiride in healthy Korean subjects.

Methods: A single 2-mg oral dose of glimepiride was administered to 46 healthy volunteers. Serial blood sampling for 12h after oral dosing was performed for determination of plasma glimepiride, glucose and insulin levels. We tested the association of seven single nucleotide polymorphisms (SNPs) in four candidate genes with the efficacy of glimepiride.

Results: Pharmacodynamic profiles for plasma glucose and insulin showed no statistically significant differences among genotype groups, and parameters were not different from one another. There were no association of the KCNJ11, NOS1AP, TCF7L2 and ABCC8 gene polymorphisms and the efficacy of glimepiride.

Conclusions: Knowledge of these polymorphisms provides no clinical useful information for the pharmacogenetic therapeutic approach for Korean patients with type 2 diabetes.