Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma.

Abstract

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.

• Authors: S Hozawa, Y Haruta, S Ishioka, M Yamakido
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 152 Issue 4 Pt 1 Pg. 1198-202 (Oct 1995) ISSN: 1073-449X [Print] United States
• PMID: 7551370 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Azepines
• Bronchoconstrictor Agents
• Platelet Activating Factor
• Platelet Aggregation Inhibitors
• Triazoles
• Methacholine Chloride
• 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

Topics

• Adult
• Analysis of Variance
• Asthma (drug therapy, physiopathology)
• Azepines (pharmacology)
• Bronchial Hyperreactivity (drug therapy, physiopathology)
• Bronchial Provocation Tests
• Bronchoconstrictor Agents
• Cross-Over Studies
• Double-Blind Method
• Female
• Forced Expiratory Volume
• Humans
• Male
• Methacholine Chloride
• Platelet Activating Factor (antagonists & inhibitors, physiology)
• Platelet Aggregation Inhibitors (pharmacology)
• Triazoles (pharmacology)