CYP2C19 GENOTYPE AND PHENOTYPE DETERMINED WITH OMEPRAZOLE IN PATIENTSWITH ACID-RELATED DISORDERS WITH AND WITHOUT HELICOBACTER-PYLORI INFECTION

Background: Omeprazole is to a major extent metabolized by cytochrome P450 isozyme CYP2C19. The aims of this study were to compare the pheno type of CYP2C19 determined by omeprazole with the genotype and to dete rmine the effect of Helicobacter pylori infection on the metabolism of omeprazole. Methods: One-hundred and forty-three Caucasian patients w ith acid-related disorders assessed with a combination of gastrointest inal symptoms and upper endoscopic findings were given 20 mg omeprazol e orally. Three hours after intake, omeprazole and 5-hydroxyomeprazole plasma concentrations were determined with high-performance liquid ch romatography, and the phenotype for metabolic capacity was expressed a s metabolic ratio (MR). Genotyping of defect alleles (CYP2C192 and *3 ) was performed by polymerase chain reaction amplification. One hundre d eleven patients were tested after the first dose of omeprazole and 3 2 patients after repetitive administration (median time, 30 days). H. pylori serology was determined with enzyme-linked immunosorbent assay at the time of phenotyping. Results: Genotypically, 2.8% had two mutat ed alleles and were poor metabolizers (PM), and 22.4% were heterozygou s extensive metabolizers (EM). Among the 111 patients who received the first omeprazole dose, 4 patients had MR >5-that is, belonged to the PM phenotype. Two of these had PM genotype (both CYP2C192/*2), and tw o had an EM genotype (CYP2C191/*1 and *1/*3), indicating that they ha ve still unidentified mutations. In the heterozygous EM group the mean MR was higher in patients who had been on continued omeprazole treatm ent than in those given the first dose (5.7 versus 2.5, P = 0.02). The re were no significant differences in MR and omeprazole concentrations between H, pylori-negative (43%) and -positive (57%) patients. Conclu sion: In all but two patients with probable unidentified mutations the re was agreement between the CYP2C19 phenotype determined by omeprazol e and the genotype. The metabolism of omeprazole in patients with acid -related disorders is genetically determined and without relation to H . pylori infection.