title: Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.
abstract: OBJECTIVE
  It has been reported that ibuprofen interferes with the antiplatelet effect of low-dose aspirin. This interaction is ascribed to steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when aspirin is administered after ibuprofen. However, whether other non-steroidal anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well defined. The aim of this study was to assess the influence of nine NSAIDs on the antiplatelet effect of aspirin.
  
  
  METHODS
  We investigated the antiplatelet effect of NSAIDs using steady-state plasma concentration reported after usual doses. We studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin before NSAID addition and aspirin after NSAID addition to platelet-rich plasma. The rates of platelet aggregation induced by collagen were determined. The final concentration of aspirin used was the 50% effective concentration (EC(50)) previously estimated in vitro.
  
  
  CONCLUSIONS
  Ibuprofen and mefenamic acid interfere with the antiplatelet effect of aspirin when added before the latter. The rate of platelet aggregation was reduced by 48·1% and 22·7%, respectively. The other NSAIDs tested did not significantly affect the aspirin antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs altered the aspirin effect if administration followed that of aspirin.
  
  
  CONCLUSIONS
  Naproxen and flurbiprofen have significant antiplatelet effects at plasma concentrations seen with usual doses. Our in vitro model suggests that the antiplatelet effect of aspirin is significantly diminished when taken after, but not before, ibuprofen or mefenamic acid. None of the other NSAIDs tested had any effect irrespective of the timing of dosing.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: N
authors.initials: N
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Soeda
authors.forename: M
authors.initials: M
authors.lastname: Ozaki
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: E
authors.initials: E
authors.lastname: Kashiwakura
authors.forename: T
authors.initials: T
authors.lastname: Kawada
authors.forename: N
authors.initials: N
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Tokuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000008:administration & dosage; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; D001241:Aspirin