Basic & Clinical Pharmacology & Toxicology 2004-09-01

Omeprazole treatment of Korean patients: effects on gastric pH and gastrin release in relation to CYP2C19 geno- and phenotypes.

Hyung-Keun Roh, Pum-Soo Kim, Don-Haeng Lee, Gunnel Tybring, Mohamed Sagar, Chang-Shin Park, Rein Seensalu, Leif Bertilsson

Index: Basic Clin Pharmacol Toxicol. 95(3) , 112-9, (2004)

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Abstract

This study aimed to investigate the effect of omeprazole on intragastric pH and gastrin release as well as the plasma concentration of omeprazole in relation to CYP2C19 genotypes after repeated doses in Korean patients. Twenty-six Korean patients with acid related disease were genotyped for CYP2C19 by allele specific PCR (wt/wt, CYP2C19*1/*1; wt/mut, CYP2C19*1/*2 or *1/*3; mut/mut, CYP2C19*2/*2, *2/*3 or *3/*3). Intragastric pH was monitored during 24 hr, and the plasma concentrations of omeprazole, hydroxyomeprazole, omeprazole sulfone and meal-stimulated gastrin were measured during 4 hr before and after 8 consecutive daily doses of 20 mg omeprazole. Unexpectedly the AUCs of omeprazole in the three genotypes were similarly high on Day 8. The mean 24 hr pH increased significantly in all three genotypes (paired t-test; P<0.0001), and the AUCs (4 hr) of gastrin in all patients increased markedly from 129+/-73 to 298+/-142 pMhr (P<0.0001). However, there was no statistically significant difference between the three genotypes in the mean pH and gastrin AUCs on Day 8. After 8 consecutive doses of 20 mg omeprazole, the gastric pH and the plasma gastrin were increased significantly in all three CYP2C19 genotypes, which were confirmed by high plasma concentrations of omeprazole in all three genotype groups. We suggest that the reason why the wt/wt had high concentrations of omeprazole similar to those in the other two genotype groups is that some of them were old with low CYP2C19 activity. In these patients omeprazole accumulated from the first to the eighth dose similar to that in the heterozygotes.