Initial 48-hour acid inhibition by intravenous infusion of omeprazole, famotidine, or both in relation to cytochrome P450 2C19 genotype status

Abstract

Backgrounds and aims: Faster and stronger acid inhibition is required for the treatment of hemorrhage from peptic ulcers. We compared the effects of intravenous infusion regimens of a proton pump inhibitor (PPI) alone, a histamine 2 receptor antagonist (H2RA) alone, and the combination of a PPI with an H2RA on acid inhibition in the early postadministration phase in relation to cytochrome P450 (CYP) 2C19 genotype status.

Methods: Fifteen Helicobacter pylori-positive volunteers with 3 different CYP2C19 genotypes were administered twice-daily intravenous infusions of 20 mg famotidine alone, 20 mg omeprazole alone, 10 mg omeprazole plus 10 mg famotidine (half-concomitant regimen), and 20 mg omeprazole plus 20 mg famotidine (full-concomitant regimen) for 2 days. The subjects underwent 48-hour intragastric pH monitoring.

Results: In homozygous extensive metabolizers (EMs) the median first 24-hour intragastric pH with the full-concomitant regimen was 4.8 (range, 4.5-5.4), which was significantly higher than that with omeprazole alone (3.9 [range, 2.6-4.7], P=.043) or famotidine alone (4.4 [range, 3.8-4.9], P=.043). In heterozygous EMs and poor metabolizers the respective median first 24-hour pH values attained with omeprazole alone (5.8 [range, 4.3-6.3] and 6.1 [range, 5.3-7.4]) and the full-concomitant regimen (5.8 [range, 5.1-6.4] and 5.8 [range, 5.4-6.2]) were significantly higher than those attained with famotidine alone (4.1 [range, 3.9-6.5] and 4.7 [range, 3.7-5.7], P=.043 for all).

Conclusions: For faster and stronger acid inhibition, the concomitant infusion regimen of a PPI and an H2RA appears to be therapeutically useful in homozygous and heterozygous EMs, but omeprazole alone appears to be sufficient in poor metabolizers of CYP2C19.