EFFECT OF BN-50730, A SPECIFIC PAF ANTAGONIST, ON PAF-INDUCED PLATELET-AGGREGATION AND SKIN-RESPONSES IN HEALTHY-HUMAN VOLUNTEERS

The effect of the oral administration of BN 50730, a specific syntheti c plate let-activating factor (PAF) receptor antagonist, on 2 recognis ed PAF-induced reactions (ex vivo platelet aggregation and immediate c utaneous responses), was assessed through 3 double-blind placebo-contr olled studies in healthy, non-allergic male volunteers. Platelet aggre gation showed a peak level of inhibition 4 hours following the single administration of either a 10, 20 or 40mg dose. A dose-response relati onship was observed regarding the duration of the effect; while lastin g less than 12 hours for the 10mg dose, inhibition was still evident 1 6 hours after administration of the 40mg dose. Wheal and flare reactio ns to intradermal PAF (400ng) were significantly inhibited following s ingle dose administration of either 10, 20 or 40mg of BN 50730. The 40 mg dose inhibited the flare reaction by more than 90% at 8 hours post- treatment. Treatment with either 20 or 40mg of BN 50730 twice daily fo r 7 days resulted in a reduction in the cutaneous responses to PAF aft er the last dose by at least 80% compared with placebo in both treatme nt groups, the 2 doses being almost equally effective. The results ind icate that BN 50730 is a potent PAF antagonist and provide interesting information for testing the product at 40 or 80mg dose levels in twic e-daily phase II clinical studies.