title: Effect of ranitidine on the antiplatelet effects of aspirin in healthy human subjects.
abstract: Aspirin is often taken with H2-receptor antagonists. In vitro data suggest that certain antagonists, such as ranitidine, have inhibitory effects on platelet function. There are no reports on the combined effect of aspirin and H2-receptor antagonists on platelet function in humans. Therefore, this study's aim was to evaluate the effects of aspirin, ranitidine, and their combination on platelet function in humans. Ten healthy men aged 34.7 +/- 2 years received aspirin 325 mg/day for 4 days followed by a 9-day washout period, 3 days of ranitidine treatment (150 mg twice daily), and 4 days of dual-drug treatment. Blood samples were drawn at baseline and on the last days of aspirin monotherapy, the washout period, ranitidine monotherapy, and dual-drug treatment. Platelet aggregation was measured in response to 0.5 mg/ml arachidonic acid, 5 and 10 mumol/L adenosine diphosphate, and 1 micro g/ml collagen. The Platelet Function Analyzer 100 test was performed, and blood salicylate levels were measured in 6 subjects. Aspirin caused a marked reduction in platelet aggregation and prolongation of Platelet Function Analyzer 100 closure time. Ranitidine caused a modest decrease in platelet aggregation. Unexpectedly, the combination of aspirin and ranitidine caused less inhibition of platelet aggregation and prolongation of Platelet Function Analyzer 100 time than aspirin alone (p = 0.02 to 0.07 compared with aspirin alone). Blood salicylate levels were lower when subjects took aspirin with ranitidine than when they took aspirin alone (1 +/- 0.8 vs 1.6 +/- 0.7 mg/dl, p = 0.005). In conclusion, ranitidine appears to attenuate the antiplatelet effects of aspirin in healthy volunteers. The most likely mechanism for these findings is a change in the absorption conditions of aspirin in the presence of ranitidine.
authors.affiliation: The Methodist Hospital Research Institute and The Methodist DeBakey Heart Center, The Methodist Hospital, Houston, TX, USA.
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
authors.forename: Ramanujam S
authors.initials: RS
authors.lastname: Ramabadran
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Guthikonda
authors.forename: Rajnikant
authors.initials: R
authors.lastname: Patel
authors.forename: Amanda
authors.initials: A
authors.lastname: Kleiman
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.forename: Timothy
authors.initials: T
authors.lastname: DeLao
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
mesh_terms: D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D006635:Histamine H2 Antagonists; D010975:Platelet Aggregation Inhibitors; D011899:Ranitidine; D001241:Aspirin