Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma

Inhaled platelet-activating factor (PAF), both in normals and in asthmatic patients, provokes transient systemic effects, neutropenia, bronchoconstriction and arterial oxygenation abnormalities similar to those shown in spontaneous exacerbations of asthma. To investigate the efficacy of a new PAF-receptor antagonist, SR 27417A, on all these changes after PAF challenge, 12 nonsmoking patients (four females and eight males) (mean+/-SEM) age 24+/-1 yrs with mild asthma (forced expiratory volume in one second (FEV1) 93+/-3% predicted) were studied in a double-blind, placebo-controlled, cross-over fashion 2 weeks apart. PAF aerosol challenge (18 microg) was carried out 3 h after oral administration of either SR 27417A (20 mg) or placebo. Respiratory system resistance (Rrs) and arterial blood gases and neutrophil cell counts were measured at baseline, before compound/placebo administration, and at 5, 15 and 45 min after PAF. Compared to vehicle, SR 27417A brought about moderate attenuation of PAF-induced neutropenia at 5 min (by 140%; p<0.025), and rebound neutrophilia at 15 and 45 min (p<0.025), increases of Rrs (by 90-65%) (p<0.01) and of alveolar-arterial pressure difference for oxygen (PA-a,O2) at 5 min (by 68%) and 15 min (by 63%), and decreases of arterial oxygen tension (Pa,O2) at 5 min (by 57%; p<0.025, each). Furthermore, systemic effects and platelet aggregation tests (p<0.001) were abolished after the administration of the compound. We conclude that SR 27417A is effective in inhibiting systemic, cellular and pulmonary effects after platelet-activating factor challenge in patients with mild bronchial asthma.

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