Prevention of gastric mucosal injury induced by anti-platelet drugs by famotidine

J Clin Pharmacol. 2014 Aug;54(8):858-64. doi: 10.1002/jcph.284. Epub 2014 Mar 21.

Abstract

Anti-platelet drug-induced gastric mucosal injury correlates with intragastric pH. Our aim was to investigate prophylaxis effects of famotidine, one of the representative histamine-2 receptor antagonists (H2RA), on gastric mucosal injury induced by dual therapy with low-dose aspirin and clopidogrel in relation to Helicobacter pylori (H. pylori) infection and CYP2C19 genotypes. This study was conducted for 20 healthy Japanese volunteers (10 H. pylori-positive and 10-negative subjects) with 100 mg aspirin plus 75 mg clopidogrel (AC) once-daily dosing and AC plus 20 mg famotidine twice-daily dosing (ACH). Mucosal injury was endoscopically assessed on day 3 and 7 and 24-hour intragastric pH and antiplatelet-function test was performed on day 7. Median pH in ACH was similar between CYP2C19 extensive metabolizer (EM) and intermediate metabolizer (IM)/poor metabolizer (PM) and was significantly higher in H. pylori-positive than negative subjects (P < .05). Mucosal injury with ACH significantly decreased in both day 3 and 7 compared with AC, irrespective with H. pylori and CYP2C19 genotypes (P < .05). Although antiplatelet effect of clopidogrel in EM was significantly higher than that in IM/PM, the additional famotidine did not affect the effect. Anti-platelet drug-induced gastric injury was alleviated by famotidine without attenuation of anti-platelet functions irrespective of H. pylori and CYP2C19 genotypes.

Keywords: H. pylori; clopidogrel; famotidine; low-dose aspirin; rabeprazole.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Ulcer Agents / administration & dosage*
  • Asian People / genetics
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics
  • Drug Therapy, Combination
  • Famotidine / administration & dosage*
  • Female
  • Gastric Acidity Determination
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / pathology
  • Genotype
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / genetics
  • Helicobacter Infections / pathology
  • Helicobacter pylori
  • Histamine H2 Antagonists / administration & dosage*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Young Adult

Substances

  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Platelet Aggregation Inhibitors
  • Famotidine
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin