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

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.