T1080 Effects of Rabeprazole Sodium and Ranitidine Hydrochloride On Gastric Acidity for 2 Consecutive Weeks: A Randomized, Open-Label, Two-Way Crossover Study in Healthy Subjects Using BRAVO ® Capsules Fixed to the Stomach

Abstract

inhibition in the early post-administration phase (48 hours) in relative to CYP2C19 genotype status. Methods: Fifteen Helicobacter pylori-positive volunteers with three different CYP2C19 genotypes were dosed with twice-daily intravenous infusions of famotidine 20 mg alone, omeprazole 20 mg alone, omeprazole 10 mg plus famotidine 10 mg (half), and omeprazole 20 mg plus famotidine 20 mg (full) for 2 days. The subjects underwent 48-hour intragastric pH monitoring. Results: With homozygous extensive metabolizers (EMs) of CYP2C19, the median first 24-hour intragastric pH with full-concomitant regimen was 4.8 (range; 4.5 5.4), which was significantly higher than that with omeprazole alone [3.9 (2.6 4.7), p = 0.043] or famotidine alone [4.4 (3.8 4.9), p = 0.043]. In heterozygous EMs and poor metabolizers, the respective median first 24-hour pHs attained by omeprazole alone [5.8 (4.3 6.3) and 6.1 (5.3 7.4)] and full-concomitant [5.8 (5.1 6.4) and 5.8 (5.4 6.2)] regimens were significantly higher than those with famotidine alone [4.1 (3.9 6.5) and 4.7 (3.7 5.7), p = all 0.043]. Conclusions: The CYP2C19 genotyping test appears to be a useful tool for determining the optimal treatment for the prevention of hemorrhage or rebleeding from peptic ulcers. If the CYP2C19 genotype status is determined before the hemorrhage, an optimal intravenous infusion regimen consisting of a PPI and an H2RA can be selected based on pharmacogenetic and pharmacogenomic status. We recommend the following intravenous infusion regimens for the faster and stronger acid inhibition: the infusion of omeprazole 20 mg alone twice-daily for PMs and heterozygous EMs, and the concomitant infusion of omeprazole 20 mg plus famotidine 20 mg twice-daily for homozygous EMs.