Effect of high-dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19

Backgrounds and Aim: Lansoprazole is mainly metabolized by cytochrome P4502 C19 (CYP2C19) in the liver. The effect of lansoprazole is assumed to be ins ufficient in subjects who are homozygous extensive metabolizers of CYP2C19. This study aimed to examine whether the CYP2C19 genotype status affected t he acid-inhibitory effects of lansoprazole and to develop a strategy to ove rcome this pharmacogenetic problem. Methods: Eighteen Helicobacter pylori-negative healthy volunteers, whose CY P2C19 genotypic status had been assessed, participated in the study. They c onsisted of 7 subjects who were homozygous extensive metabolizers, 7 subjec ts who were heterozygous extensive metabolizers, and 4 subjects who were po or metabolizers of CYP2C19, who took a placebo or lansoprazole 30 mg once d aily in the morning for 8 days. On day 8 of closing, 24-hour intragastric p H values were recorded. Five of the homozygous extensive metabolizer subjec ts underwent the 24-hour intragastric pH monitoring on day 8 of dosing of l ansoprazole 30 mg 4 times daily. Results: When lansoprazole 30 mg was given once daily, the mean 24-hour int ragastric pH values in the subjects who were homozygous extensive metaboliz ers, heterozygous extensive metabolizers, and poor metabolizers were 4.5, 4 .9, and 5.5, respectively (P < .005). On day 8 of dosing of lansoprazole 30 mg 4 times daily in subjects who were homozygous extensive metabolizers, t he mean 24-hour intragastric pH value was 7.4. Conclusion: The effect of lansoprazole on intragastric pH depended signific antly on CYP2C19 genotype status. Complete acid inhibition could be achieve d by the frequent administration of lansoprazole (eg, 30 mg 4 times daily) in subjects who were homozygous extensive metabolizers. A genotyping test o f CYP2C19 status appears useful for prescribing an optimal dosing scheme of lansoprazole.