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CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans*
- Source :
- Clinical Pharmacology & Therapeutics; May 1999, Vol. 65 Issue: 5 p552-561, 10p
- Publication Year :
- 1999
-
Abstract
- Objective: Omeprazole is metabolized by genetically determined S-mephenytoin 4′-hydroxylase (CYP2C19) in the liver. This study aimed to determine whether the effect of omeprazole on intragastric pH depends on CYP2C19 genotype status.Methods: CYP2C19 genotype status for 2 mutations associated with the poor metabolizer phenotype was determined by a polymerase chain reaction–restriction fragment length polymorphism method in 16 healthy volunteers. Helicobacter pylori status was determined by serology and the [13C]urea breath test. After a single oral administration of 20 mg omeprazole or a placebo, intragastric 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, 10, and 24 hours after administration.Results: Fifteen of the 16 subjects were H pylori negative. Five of the 15 subjects were homozygous extensive metabolizers, 4 were heterozygous extensive metabolizers, and 6 were poor metabolizers. After omeprazole administration, significant differences in mean intragastric pH values and plasma levels of gastrin, omeprazole and its metabolites were observed among the 3 groups, whereas no significant differences in these parameters were observed with the placebo administration.Conclusions: The effect of omeprazole on intragastric pH significantly depends on CYP2C19 genotype status. The genotyping test of CYP2C19 may be useful for an optimal prescription of omeprazole.
Details
- Language :
- English
- ISSN :
- 00099236 and 15326535
- Volume :
- 65
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Clinical Pharmacology & Therapeutics
- Publication Type :
- Periodical
- Accession number :
- ejs19518641
- Full Text :
- https://doi.org/10.1016/S0009-9236(99)70075-5