The effect of nimesulide versus placebo on hemostasis in healthy volunteers.
OBJECTIVE
The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective.


METHODS
A randomised, double-blind, placebo-controlled, parallel group, single centre study performed on 20 healthy male volunteers who received either placebo or nimesulide 100 mg twice daily for 7 days. Bleeding time, platelet count and platelet aggregation, thromboplastin time (prothrombin time), activated partial thromboplastin time, fibrinogen, Factor VIII:C, vWF:Ag, vWF:RCof and platelet-rich plasma aggregation following stimulation with adenosine 5'-diphosphate, collagen, arachidonic acid, ristocetin, thrombin and thrombin receptor-activating peptide were measured at baseline (day 0), and then 3 h after the first (day 1) and last (day 7) treatment.


RESULTS
The bleeding times for all subjects remained within the normal range throughout the study period, with no significant differences between the two treatment groups. There were no significant changes from baseline in platelet aggregation studies or in any of the other haemostasis tests, with no significant differences between the two groups. No clinically significant adverse events were reported or observed.


CONCLUSIONS
Daily administration of 200 mg nimesulide for 7 days neither prolongs bleeding time nor modifies any of the other haemostasis variables measured. The lack of interactions with important haemostatic mechanisms suggests that nimesulide may also be used in patients with bleeding problems. This expectation has still to be confirmed by clinical experience.
Marbet
G A
GA
Hämostaselabor DZL, Kantonsspital Basel, Switzerland.
Yasikoff Strub
M L
ML
Macciocchi
A
A
Tsakiris
D A
DA
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D001760:Bleeding Time; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010919:Placebos; D010974:Platelet Aggregation / Q000187:drug effects; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D013449:Sulfonamides; D014841:von Willebrand Factor; C012655:nimesulide