EFFECTS OF KETOPROFEN AND IBUPROFEN ON PLATELET-AGGREGATION AND PROSTANOID FORMATION IN MAN

Objective: In the present randomized, four-way crossover study we dete rmined the effects of two oral doses each of ketoprofen and ibuprofen on platelet aggregation and prostanoid formation in man. Methods: Twel ve healthy female volunteers received for 2 consecutive days, followed by a 5-day drug-free interval, one of the following: ketoprofen 3 x 2 5 mg per day, or ketoprofen 3 x 50 mg per day, or ibuprofen 3 x 200 mg per day, or ibuprofen 3 x 400 mg per day. The response criteria, dete rmined before and on the 2nd day of each treatment period, were: maxim al platelet aggregation in response to 1.0 mmol . l(-1) arachidonic ac id measured by the method of Born and Cross, thromboxane B-2 (TXB(2)) concentration in platelet-rich plasma after aggregation measured by ra dioimmunoassay, and PGE-PM, the index metabolite of total body prostag landin E(2) (PGE(2)) production, assessed by gas chromatography/tandem mass spectrometry using O-18(2)-PGE-M as internal standard. Results: Platelet aggregation was significantly reduced by ketoprofen 3 x 25 mg per day (-57%) and ketoprofen 3 x 50 mg per day (-85%) as compared to control, whereas ibuprofen 3 x 200 mg per day (-3%) and ibuprofen 3 x 400 mg per day (-22%) had no significant effects. TXB(2) synthesis wa s significantly decreased by ketoprofen 3 x 25 mg per day (-72%), keto profen 3 x 50 mg per day (-97%) and ibuprofen 3 x 400 mg per day (-48% ) as compared to control; ibuprofen 3 x 200 mg per day did not reduce TXB(2) formation significantly (-23%). All four treatments reduced 24- h urinary excretion of PGE-M significantly in the range of -39% (ketop rofen 3 x 25 mg per day) to -53% (ibuprofen 3 x 400 mg per day) withou t significant differences between treatments. Conclusion: Our data sho w that both ketoprofen dosages were more effective in inhibition of pl atelet aggregation and platelet thromboxane synthesis than ibuprofen i n low or high dosage. Total body synthesis of the E-prostaglandins was inhibited by all drug schedules without significant differences betwe en treatments.