Inhibition of cutaneous and platelet responses to platelet-activating factor by oral WEB 2086 in man.

WEB 2086, an antagonist of platelet-activating factor (PAF), was assessed against the cutaneous response in vivo and the aggregation of platelets ex vivo induced by PAF in a double-blind, placebo-controlled, crossover study in 12 normal male volunteers. Wheal-and-flare responses to intradermal PAF (200 ng) and histamine (1 microgram) were measured 1 hour after placebo or control administration. Wheal volumes were significantly reduced by 66% +/- 8.7% (mean +/- SEM), 86% +/- 8.3%, and 90% +/- 6.0% after 10, 40, and 100 mg of WEB 2086 compared to placebo administration (p less than 0.005). Flare responses were correspondingly inhibited by 66% +/- 8.3%, 82% +/- 8.7%, and 84% +/- 7.8% at 10, 40, and 100 mg of WEB 2086, respectively. Cutaneous responses to histamine were unaffected. Ex vivo platelet responses to PAF were significantly inhibited at all three doses of WEB 2086. Oral WEB 2086 is a potent and specific inhibitor of cutaneous and platelet responses to PAF in man.