Impact of cytochrome P450 CYP2C9 variant allele CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjects

AimTo investigate the impact of CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam. MethodsCYP2C9*3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9*1/*3 genotype and 11 with *1/*1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately. ResultsAfter a single oral dose of 2.5 mg glibenclamide, C_max was (70.0±11.5) μg·L^-1 in CYP2C9*1/*3 subjects and (51.9±12.3) μg·L^-1 in *1/*1 subjects. AUC_0-∞ were (435±47) vs (287±95) μg·h·L^-1 (in *1/*3 vs *1/*1 subjects), and CL/F were (96±9.3) vs (160±51) mL·min^-1, respectively. Statistic analysis results indicated that glibenclamide AUC0-∞ was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9*1/*3 subjects than those in *1/*1 subjects (P<0.01). After a single oral dose of 8 mg lornoxicam, C_max was (1.54±0.24) mg·L^-1 in CYP2C9*1/*3 subjects and (1.19±0.37) mg·L^-1 in *1/*1 subjects. AUC_0-∞ were (14.9±2.2) vs (6.92±1.48) mg·h·L^-1 (in *1/*3 vs *1/*1 subjects), and CL/F were (9.1±1.2) vs (20.1±4.6) mL·min^-1, respectively. Statistic analysis results indicated that lornoxicam AUC_0-∞ was significantly higher (2.2-fold) and subsequently CL/F was significantly lower (55%) in CYP2C9*1/*3 subjects than those in *1/*1 subjects (P<0.001). ConclusionCYP2C9*3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9*1/*3 genotype, especially lornoxicam.