BACKGROUND: Omeprazole is to a major extent metabolized by cytochrome P450 isozyme CYP2C19. The aims of this study were to compare the phenotype of CYP2C19 determined by omeprazole with the genotype and to determine the effect of Helicobacter pylori infection on the metabolism of omeprazole. METHODS: One-hundred and forty-three Caucasian patients with acid-related disorders assessed with a combination of gastrointestinal symptoms and upper endoscopic findings were given 20 mg omeprazole orally. Three hours after intake, omeprazole and 5-hydroxyomeprazole plasma concentrations were determined with high-performance liquid chromatography, and the phenotype for metabolic capacity was expressed as metabolic ratio (MR). Genotyping of defect alleles (CYP2C19*2 and *3) was performed by polymerase chain reaction amplification. One hundred eleven patients were tested after the first dose of omeprazole and 32 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 mutated alleles and were poor metabolizers (PM), and 22.4% were heterozygous 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 CYP2C19*2/*2), and two had an EM genotype (CYP2C19*11*1 and *1/*3), indicating that they have still unidentified mutations. In the heterozygous EM group the mean MR was higher in patients who had been on continued omeprazole treatment than in those given the first dose (5.7 versus 2.5, P = 0.02). There were no significant differences in MR and omeprazole concentrations between H. pylori-negative (43%) and -positive (57%) patients. CONCLUSION: In all but two patients with probable unidentified mutations there was agreement between the CYP2C19 phenotype determined by omeprazole and the genotype. The metabolism of omeprazole in patients with acid-related disorders is genetically determined and without relation to H. pylori infection.
BACKGROUND:Omeprazole is to a major extent metabolized by cytochrome P450 isozyme CYP2C19. The aims of this study were to compare the phenotype of CYP2C19 determined by omeprazole with the genotype and to determine the effect of Helicobacter pylori infection on the metabolism of omeprazole. METHODS: One-hundred and forty-three Caucasian patients with acid-related disorders assessed with a combination of gastrointestinal symptoms and upper endoscopic findings were given 20 mg omeprazole orally. Three hours after intake, omeprazole and 5-hydroxyomeprazole plasma concentrations were determined with high-performance liquid chromatography, and the phenotype for metabolic capacity was expressed as metabolic ratio (MR). Genotyping of defect alleles (CYP2C19*2 and *3) was performed by polymerase chain reaction amplification. One hundred eleven patients were tested after the first dose of omeprazole and 32 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 mutated alleles and were poor metabolizers (PM), and 22.4% were heterozygous 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 CYP2C19*2/*2), and two had an EM genotype (CYP2C19*11*1 and *1/*3), indicating that they have still unidentified mutations. In the heterozygous EM group the mean MR was higher in patients who had been on continued omeprazole treatment than in those given the first dose (5.7 versus 2.5, P = 0.02). There were no significant differences in MR and omeprazole concentrations between H. pylori-negative (43%) and -positive (57%) patients. CONCLUSION: In all but two patients with probable unidentified mutations there was agreement between the CYP2C19 phenotype determined by omeprazole and the genotype. The metabolism of omeprazole in patients with acid-related disorders is genetically determined and without relation to H. pyloriinfection.
Authors: Eileen B Lawson; Jerry C Wu; R Michael Baldwin; Magnus Ingelman-Sundberg; Staffan Rosenborg; Dong-Seok Yim; Ophelia Q P Yin; Edmund V Capparelli; Joseph D Ma Journal: Eur J Clin Pharmacol Date: 2011-10-19 Impact factor: 2.953
Authors: Sushil K Ahlawat; Raja Mohi-Ud-Din; Dionne C Williams; Kathleen A Maher; Stanley B Benjamin Journal: Dig Dis Sci Date: 2005-11 Impact factor: 3.199
Authors: Sunny Park; Yang Jin Hyun; Yu Ran Kim; Ju Hyun Lee; Sunae Ryu; Jeong Mi Kim; Woo Yong Oh; Han Sung Na; Jong Gu Lee; Doo Won Seo; In Yeong Hwang; Zewon Park; In Jin Jang; Jaeseong Oh; Seung Eun Choi Journal: J Korean Med Sci Date: 2017-05 Impact factor: 2.153