Initial 48-hour acid inhibition by intravenous infusion of omeprazole, famotidine, or both in relation to cytochrome P450 2C19 genotype status.
OBJECTIVE
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.
Sugimoto
Mitsushige
M
First Department of Medicine and Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan. mitsu@hama-med.ac.jp
Furuta
Takahisa
T
Shirai
Naohito
N
Ikuma
Mutsuhiro
M
Hishida
Akira
A
Ishizaki
Takashi
T
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015738:Famotidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005745:Gastric Acidity Determination; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016037:Single-Blind Method; D013997:Time Factors
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D015738:Famotidine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole