The clinical relevance of CYP2C19 genotype status on the rational drug treatment

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The genetic polymorphism of CYP2C19 has been recognized. The marked interethnic differences in the incidence of poor metabolizers (PM) of CYP2C19 have been reported ; 2-4% in Caucaisian, 15-20% in Japanese. Proton pump Inhibiter (PPI) such us omeprazole (OPZ), which have been widely used in the upper gastroduodenal diseases, is mainly metabolized by CYP2C19. Therefore, the aim of this study is to examine the clinical relevance of CYP2C19 genotype status on the eradication therapy of H.pylori.Study 1 : Intragastric pH values were recorded for 24 hours in 15 healthy volunteers after a 20 mg of omeprazole or a placebo. Plasma levels of omeprazole and its 2 metabolites and gastrin were measured throughout 24 hours after administration. 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 (homEM, hetEM, PM), whereas no significant differences in these parameters were observed with the placebo.Study 2 : Sixty two patients with peptic ulcer and H.pylori infection underwent the dual therapy with 20 mg of omeprazole once a day and 500 mg of amoxicillin qid for 2 weeks. At one month after the dual treatment, cure of H.pylori infection was assessed on the basis of history, a rapid urease test, culture, PCR and 13C-urea breath test. Cure of H.pylori infection was achieved in 32 of the 62 patients (51.6%). Cure rates for H.pylori infection were clearly dependent on CYP2C19 genotype status : homEM, hetEM, and PM groups were 28.6%, 60.0%, and 100%, respectively.The genotyping test for CYP2C19 is useful for the rational eradication therapy of H.pylori.