C Upsilon P2C19 genotype status and effect of omeprazole on intragastric pH in humans

Citation
T. Furuta et al., C Upsilon P2C19 genotype status and effect of omeprazole on intragastric pH in humans, CLIN PHARM, 65(5), 1999, pp. 552-561
Citations number
51
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
65
Issue
5
Year of publication
1999
Pages
552 - 561
Database
ISI
SICI code
0009-9236(199905)65:5<552:CUPGSA>2.0.ZU;2-2
Abstract
Objective: Omeprazole is metabolized by genetically determined S-mephenytoi n 4'-hydroxylase (CYP2C19) in the liver. This study aimed to determine whet her the effect of omeprazole on intragastric pH depends on CYP2C19 genotype status. Methods: CYP2C19 genotype status for 2 mutations associated with the poor m etabolizer phenotype was determined by a polymerase chain reaction-restrict ion fragment length polymorphism method in 16 healthy volunteers. Helicobac ter pylori status was determined by serology and the [C-13]urea breath test . After a single oral administration of 20 mg omeprazole or a placebo, intr agastric pH values were recorded for 24 hours. Plasma levels of omeprazole and its 2 metabolites and gastrin were measured before and 1, 2, 3, 5, 7, 1 0, and 24 hours after administration. Results:Fifteen of the 16 subjects were H pylori negative. Five of the 15 s ubjects were homozygous extensive metabolizers, 4 were heterozygous extensi ve metabolizers, and 6 were poor metabolizers. After omeprazole administrat ion, significant differences in mean intragastric PH values and plasma leve ls of gastrin, omeprazole and its metabolites were observed among the 3 gro ups, whereas no significant differences in these parameters were observed w ith the placebo administration. Conclusions: The effect of omeprazole on intragastric pH significantly depe nds on CYP2C19 genotype status. The genotyping test of CYP2C19 may be usefu l for an optimal prescription of omeprazole.