Interactions between aspirin and COX-2 inhibitors or NSAIDs in a rat thrombosis model.
Recent in vitro studies, clinical trials and epidemiological studies have suggested possible interactions between aspirin and other cyclo-oxygenase (COX) inhibitors, such as ibuprofen of the COX-2 inhibitors celecoxib and rofecoxib. The objective of this study was to test the effects of aspirin (1, 2.5 and 5 mg/kg), and ibuprofen (4 and 15 mg/kg), diclofenac (2.5 mg/kg), flurbiprofen (2 mg/kg), celecoxib (7.5 mg/kg), and rofecoxib (1 mg/kg), alone or combined on a rat model of arterial thrombosis. Drugs were given orally daily for 7 days, before insertion of an arterio-venous shunt thrombosis system, left in place for 15 min. Main parameter was thrombus weight. Five to 12 rats were used per experiment, and 35 controls overall. Aspirin inhibited thrombus formation in a dose-dependent manner. All NSAIDS given alone also inhibited thrombus formation to approximately the same level as aspirin 1 mg/kg/day. Ibuprofen, celecoxib and rofecoxib inhibited the effects of aspirin, but not diclofenac or flurbiprofen. The interactions with aspirin do not seem to affect all NSAIDs to equal levels. The clinical impact of this needs to be confirmed in adequately powered clinical trials or pharmaco-epidemiological studies.
Department of Pharmacology, Université Victor Segalen, 33076 Bordeaux, France.
Anwar
A
Umar
Michel
M
Boisseau
Abdiryim
A
Yusup
Halmurat
H
Upur
Bernard
B
Bégaud
Nicholas
N
Moore
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005480:Flurbiprofen / Q000008:administration & dosage / Q000009:adverse effects; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects; D013927:Thrombosis / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D004008:Diclofenac; D005480:Flurbiprofen; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D001241:Aspirin; D007052:Ibuprofen