Rofecoxib exerts no effect on platelet plug formation in healthy volunteers.

OBJECTIVE: Although rofecoxib has very high selectivity for cyclo-oxygenase 2 (COX-2), supratherapeutic rofecoxib concentrations (> 1000 mg) inhibit purified human COX-1 in vitro and TXB2 formation in vivo. It is therefore possible that higher doses of rofecoxib may affect platelet function. This could be important if rofecoxib is given to thrombocytopenic patients. In these cases, already moderate inhibition of platelet function could precipitate bleeding complications. We therefore set out to investigate the influence of rofecoxib on platelet function in healthy volunteers. METHODS: We set up a balanced-randomised, double-blind, placebo-controlled, two way cross-over study. Peripheral blood was withdrawn from 42 healthy volunteers before and 3 hours after intake of 50, 250, 500 mg of rofecoxib or placebo (n = 14 per group). Platelet function was assessed by a platelet function analyzer (PFA-100) which measures collagen-epinephrine induced closure time (CEPI-CT) under shear stress. RESULTS: CEPI-CT increased by 14% (p = 0.002) and 11% (p = 0.003) three hours after intake of placebo and rofecoxib at dosages of up to 500 mg, respectively. The increase in CEPI-CT versus baseline was not significantly different in the placebo period compared with the active treatment periods (n = 42, p > 0.05). CONCLUSIONS: Rofecoxib does not impair platelet function. Thus, rofecoxib appears to be a valuable analgetic and antipyretic agent in the therapy of patients at risk for bleeding.