The effect of CYP2C19 polymorphism on the pharmacokinetics and acid-inhibitory effects of oral lansoprazole and omeprazole

Abstract

Lansoprazole (LPZ) and omeprazole (OPZ) are metabolized by CYP2C19 and CYP3A4. The major metabolic pathway for OPZ is hydroxylation by CYP2C19. The aim of the study was to compare the effect of CYP2C19 genotype status on pharmacokinetics and acid-inhibitory effects of LPZ with that of OPZ. A randomized three-way crossover study was performed in 12 H. pylori-negative healthy Caucasian subjects. Subjects received OPZ 10 mg o.d. and LPZ 15 mg o.d. for 7 days with a 2-week washout period. Plasma concentrations of LPZ and OPZ were measured at day 1, and gastric pH was monitored at day 1 and 6 of drug administration. CYP2C19 genotype was determined by a PCR-RFLP method. CYP2C19 status was determined in 11 subjects; six were homozygous extensive metabolizers (homEMs) and five were heterozygous extensive metabolizers (hetEMs). There were no significant differences between hetEMs and homEMs in median 24 h gastric pH and % of time pH > 4 during the baseline period. At day 1 of OPZ administration area under the concentration time curve (AUC) and acid-inhibitory effect (median 24 h pH) were significantly greater in hetEMs than in homEMs (Table 1). At day 1 of LPZ administration AUC and acid-inhibitory effect were not significantly different between hetEMs and homEMs, although there was a trend towards an increased AUC and acid-inhibitory effect in hetEMs. Therefore we compared the acid-inhibitory effect of LPZ and OPZ to baseline. Table 1 Median (25; 75percentile), nonparametric analysis. Compared with baseline median 24 h pH and % of time pH > 4 at day 1 were significantly increased in hetEMs, but not in homEMs for both LPZ and OPZ. At day 6 the differences in acid-inhibitory effect between hetEMs and homEMs were not significant. At day 1 of administration acid inhibitory effect of LPZ 15 mg and OPZ 10 mg is affected by CYP2C19 polymorphism. Compared with baseline, there was at day 1 a significant acid-inhibitory effect in hetEMs, but not in homEMs.