CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability

Citation
T. Kita et al., CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability, PHARM RES, 18(5), 2001, pp. 615-621
Citations number
31
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACEUTICAL RESEARCH
ISSN journal
07248741 → ACNP
Volume
18
Issue
5
Year of publication
2001
Pages
615 - 621
Database
ISI
SICI code
0724-8741(200105)18:5<615:CGREOO>2.0.ZU;2-7
Abstract
Purpose. A combination of proton pump inhibitors and antimicrobials has bee n applied as an anti-Helicobncrer pylori (N. pylori) therapy. Omeprazole, o ne of the proton pump inhibitors, is metabolized by CYP2C19, which exhibits genetic polymorphism. It was reported previously that the overall anti-H. pylori efficacy can be related to the CYP2C19 genotype. The main aim of the present study was to obtain a rational explanation for the relationship be tween the overall anti-H. pylori efficacy and the CYP2C19 genotype. Methods. Six healthy volunteers were classified as extensive metabolizers a nd poor metabolizers, according to their CYP2C19 genotypes. Plasma concentr ations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole. The stability of amoxicillin, clarithr omycin, and metronidazole was examined using buffer solutions with monitore d intragastric pH, and their remaining percentage in the intragastric space was simulated. Results. The poor metabolizers, classified by the CYP2C19 genotypes, showed the higher effectiveness in anti-H. pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly th e higher stability of antimicrobials in the higher intragastric pH. Conclusions. CYP2C19 genotyping is a very useful method to determine the ef fective and safe dosage regimen including the selection of the dual and tri ple therapy in anti-H. pylori therapy.