Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma.
The involvement of platelet-activating factor (PAF) in bronchial hyperresponsiveness (BHR) in bronchial asthma has been controversial. To determine whether PAF is involved in BHR in humans, we carried out a randomized, double-blind, placebo-controlled, two-phase cross-over study on the effects of Y-24180, a potent, specific, orally active PAF receptor antagonist, on BHR to methacholine in patients with asthma. The subjects were 13 patients with extrinsic stable asthma. The provocative concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1) 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 of cross-over from the first treatment regimen to the second regimen, administration of the test drug was suspended for 2 wk. The methacholine challenge test was performed four times, before and after the first treatment period and before and after the second treatment period. Compared with the placebo, Y-24180 significantly (p = 0.005) improved the PC20-FEV1 value without carryover effect and period effect by analysis of variance. These results suggest that PAF is an important mediator involved in the BHR of bronchial asthma in humans.
Hozawa
S
S
2nd Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Haruta
Y
Y
Ishioka
S
S
Yamakido
M
M
D000328:Adult; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001381:Azepines / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D016085:Bronchoconstrictor Agents; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D016210:Methacholine Chloride; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine