Effect of BN 50730, a Specific PAF Antagonist, on PAF-Induced Platelet Aggregation and Skin Responses in Healthy Human Volunteers
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The effect of the oral administration of BN 50730, a specific synthetic plate-let-activating factor (PAF) receptor antagonist, on 2 recognised PAF-induced reactions (ex vivo platelet aggregation and immediate cutaneous responses), was assessed through 3 double-blind placebo-controlled studies in healthy, non-allergic male volunteers. Platelet aggregation showed a peak level of inhibition 4 hours following the single administration of either a 10, 20 or 40mg dose. A dose-response relationship was observed regarding the duration of the effect; while lasting less than 12 hours for the 10mg dose, inhibition was still evident 16 hours after administration of the 40mg dose. Wheal and flare reactions to intradermal PAF (400ng) were significantly inhibited following single dose administration of either 10, 20 or 40mg of BN 50730. The 40mg 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 for 7 days resulted in a reduction in the cutaneous responses to PAF after the last dose by at least 80% compared with placebo in both treatment groups, the 2 doses being almost equally effective. The results indicate that BN 50730 is a potent PAF antagonist and provide interesting information for testing the product at 40 or 80mg dose levels in twice-daily phase II clinical studies.
KeywordsPlatelet Aggregation Platelet Activate Factor Drug Invest Induce Platelet Aggregation Cutaneous Response
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