Parecoxib Sodium does not Impair Platelet Function in Healthy Elderly and Non-Elderly Individuals Two Randomised, Controlled Trials

摘要

Objective: To compare the effects of parecoxib sodium, an injectable prodrug of a cyclo-oxygenase-2-specific inhibitor, and ketorolac on platelet function and bleeding time in elderly individuals and non-elderly adults.Design and Setting: Double-blind, randomised, active- and placebo-controlled, parallel-group studies.Patients and Participants: Healthy men and women, between the ages of 65 and 95 years (62 elderly individuals) or 18 and 55 years (48 non-elderly individuals).Methods:Participants received placebo or active medication: parecoxib sodium 40mg twice daily intravenously for 8 days (both studies), ketorolac 15mg four times daily intravenously for 5 days (elderly individuals) or 30mg four times daily intravenously for 5 days (non-elderly individuals). Ex vivo platelet aggregation responses to arachidonate, collagen and adenosine diphosphate (ADP), bleeding time and serum thromboxane B_2 (T_xB_2) levels were measured.Results: In both studies, parecoxib sodium had little or no effect on arachidonate-induced platelet aggregation, whereas ketorolac caused statistically significant and sustained decreases in platelet aggregation throughout the entire drug administration period. Parecoxib sodium also had little or no effect on collagen- or ADP-induced aggregation compared with ketorolac. Although there was a high degree of variability in bleeding times, significant prolongation of bleeding times was observed only in the ketorolac groups in both studies. Parecoxib sodium had no effect on serum T_xB_2 concentrations in non-elderly individuals. In elderly individuals, ketorolac significantly and profoundly reduced TxB2 levels at all assessments, whereas parecoxib sodium showed less of a reduction.Conclusion: Although a direct correlation has not been proven, patients with reduced platelet function do appear to be at a higher risk of experiencing increased bleeding during surgery. Thus, the absence of effect on platelet aggregation and bleeding time observed in these studies suggests that parecoxib sodium is less likely to be associated with excessive bleeding during surgery, and therefore is potentially safer than ketorolac for use in patients undergoing surgery, irrespective of age.