Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects

Arch Pharm Res. 2023 May;46(5):438-447. doi: 10.1007/s12272-023-01448-z. Epub 2023 Apr 25.ABSTRACTGliclazide metabolism is mediated by genetically polymorphic CYP2C9 and CYP2C19 enzymes. We investigated the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide. Twenty-seven Korean healthy volunteers were administered a single oral dose of gliclazide 80 mg. The plasma concentration of gliclazide was quantified for the pharmacokinetic analysis and plasma concentrations of glucose and insulin were measured as pharmacodynamic parameters. The pharmacokinetics of gliclazide showed a significant difference according to the number of defective alleles of combined CYP2C9 and CYP2C19. The two defective alleles group (group 3) and one defective allele group (group 2) showed 2.34- and 1.46-fold higher AUC0-∞ (P < 0.001), and 57.1 and 32.3% lower CL/F (P < 0.001), compared to those of the no defective allele group (group 1), respectively. The CYP2C9IM-CYP2C19IM group had AUC0-∞ increase of 1.49-fold (P < 0.05) and CL/F decrease by 29.9% (P < 0.01), compared with the CYP2C9 Normal Metabolizer (CYP2C9NM)-CYP2C19IM group. The CYP2C9NM-CYP2C19PM group and CYP2C9NM-CYP2C19IM group showed 2.41- and 1.51-fold higher AUC0-∞ (P < 0.001), and 59.6 and 35.4% lower CL/F (P < 0.001), compared to those of the CYP2C9NM-CYP2C19NM group, respectively. The results represented that CYP2C9 and CYP2C19 genetic polymorphisms signi...
Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Source Type: research