title: Influence of nonsteroidal anti-inflammatory drugs on aspirin's antiplatelet effects and suggestion of the most suitable time for administration of both agents without resulting in interaction.
abstract: BACKGROUND
  Low-dose aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1) and suppresses platelet aggregation. It is effective for secondary prevention of cardiovascular events. Because nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly bind with COX-1, the antiplatelet effects of aspirin may be suppressed when NSAIDs are co-administered. This interaction could be avoided by avoiding simultaneous administration; however, the minimum interval that should separate the administration of aspirin and loxoprofen is not well known. In this study, we investigated how to avoid the influence of NSAIDs on the antiplatelet effects of aspirin. An in vitro experiment was performed to investigate the influence of ibuprofen and loxoprofen at various concentrations on aspirin's antiplatelet action.
  
  
  METHODS
  Platelet aggregation and thromboxane B2(TXB2) levels were measured after addition of aspirin only and NSAIDs plus aspirin to platelet-rich plasma. NSAIDs were used at their maximum plasma concentrations, the assumed concentration after 6 h (for loxoprofen only), and the assumed concentration after 12 h of taking one clinical dose. Platelet aggregation threshold index (PATI), defined as the putative stimulus concentration giving 50% aggregation, was calculated as an index of aggregation activity.
  
  
  RESULTS
  PATI decreased in ibuprofen plus aspirin group compared to that in the aspirin only group, regardless of ibuprofen concentration. Furthermore, PATI significantly decreased when aspirin was added after loxoprofen-trans-OH addition at the maximum concentration (4.1 ± 0.1 μg/mL), compared to that in aspirin only group (5.9 ± 0.1 μg/mL). PATI showed no significant difference after addition of loxoprofen at the assumed concentration after 6 h (aspirin only group, 5.0 ± 0.5 μg/mL; loxoprofen-trans-OH plus aspirin group, 4.9 ± 0.4 μg/mL).In addition, TXB2concentration tended to decrease with increasing PATI.
  
  
  CONCLUSIONS
  It is desirable to avoid ibuprofen co-administration with the usual once-daily low-dose aspirin therapy; however, a 6-h interval between loxoprofen and aspirin could avoid this potential interaction when loxoprofen is taken before aspirin.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.|Department of Pharmacy, Koshigaya Municipal Hospital, 10-47-1 Higashi-Koshigaya, Koshigaya, Saitama 343-0023 Japan.
authors.forename: Kenta
authors.identifier: 0000-0002-6099-7346
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Pharmacy, National Hospital Organization, Yokohama Medical Center, 3-60-2 Harajuku, Totsuka, Yokohama, Kanagawa 245-8575 Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Akagi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Nozawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.|Department of Pharmacy, Chemotherapy Research Institute, Kaken Hospital, 6-1-14 Konodai, Ichikawa, Chiba 272-0827 Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimomura
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Aoyama
keywords: Antiplatelet; Aspirin; Coating; Cyclooxygenase-1; Drug interaction; Human; Ibuprofen; Loxoprofen; Nonsteroidal anti-inflammatory drugs; Platelet aggregation threshold index