EFFECTS OF A PAF ANTAGONIST, Y-24180, ON BRONCHIAL HYPERRESPONSIVENESS IN PATIENTS WITH ASTHMA

The involvement of platelet-activating factor (PAF) in bronchial hyper responsiveness (BHR) in bronchial asthma has been controversial. To de termine whether PAF is involved in BHR in humans, we carried out a ran domized, double-blind, placebo-controlled, two-phase cross-over study on the effects of Y-24180, a potent, specific, orally active PAF recep tor antagonist, on BHR to methacholine in patients with asthma. The su bjects were 13 patients with extrinsic stable asthma. The provocative concentration of methacholine producing a 20% fall in FEV(1) (PC20-FEV (1)) was measured as an index of BHR. Y-24180 (20 mg twice a day) or a placebo was orally administered for 2 wk, respectively. At the time o f cross-over from the first treatment regimen to the second regimen, a dministration of the test drug was suspended for 2 wk. The methacholin e challenge test was performed four times, before and after the first treatment period and before and after the second treatment period. Com pared with the placebo, Y-24180 significantly (p = 0.005) improved the PC20-FEV(1) value without carryover effect and period effect by analy sis of variance. These results suggest that PAF is an important mediat or involved in the BHR of bronchial asthma in humans.