COMBINED EFFECT OF WEB-2086 (PAF ANTAGONIST) AND KETOPROFEN (NSAID) ON PAF-INDUCED EX-VIVO PLATELET-AGGREGATION IN BOVINE

The effect of the specific PAF-antagonist WEB 2086, a thieno-triazolo- diazepine, and ketoprofen, a NSAID, was investigated on PAF-induced bo vine platelet aggregation measured ex vivo in platelet-rich plasma (PR P). WEB 2086 was infused intravenously over 1 min followed immediately by ketoprofen administration over 1 s (both drugs = 3 mg/kg), in a gr oup of six healthy male Friesian calves. Depending on the PAF concentr ation, a reversible (10(-8)-10(-9) mol/l) and irreversible (10(-5)-10( -7) mol/l) platelet aggregation was observed. The reversible aggregati on was completely blocked by pretreatment of the animal with WEB 2086 and ketoprofen. The inhibitory effects observed during the irreversibl e aggregation were 47.22%, 54.00% and 88.00% at 10(-5), 10(-6) and 10( -7) mol/l PAF, respectively Moreover, the aggregation obtained in thes e condition became reversible. Maximal inhibitory effect of WEB 2086 a nd ketoprofen on PAF-induced platelet aggregation in calves was observ ed within 30 min after administration of both drugs. This inhibition p ersisted even after 24 h and was significantly different from control with P < 0.05. The combined effect of both drug exceeded the sum of th e individual effects (synergism). It was concluded that WEB 2086 and k etoprofen very effectively blocked PAF-induced bovine platelet aggrega tion in platelet-rich plasma. The study also suggested a synergism bet ween both substances.