The effect of GR32191 (a thromboxane receptor antagonist) on airway responsiveness in asthma.
Airway responsiveness to methacholine was measured in nine subjects (22-53 years, seven male) with chronic stable asthma. All subjects were taking inhaled beclomethasone (less than 1000 micrograms daily). The mean baseline FEV1 was 2.841 (77% of predicted) and the geometric mean PD20FEV1 was 31 micrograms. After a run-in period, the subjects were randomly allocated to two treatment periods with the specific thromboxane receptor antagonist GR32191, 40 mg four times daily for 3 weeks, and identical placebo capsules. A double-blind, placebo-controlled, cross-over design was employed with 4 weeks between the two treatment periods. Treatment with GR32191 did not result in any significant improvement in mean FEV1 (2.941 after placebo and 2.861 after GR3219; F7.71 = 1.02, P greater than 0.1) or PD20FEV1 (24.3 micrograms after placebo and 38.5 micrograms after GR32191; F7.71 = 0.59, P greater than 0.1). We conclude that thromboxane is not important in the maintenance of airway hyperresponsiveness in chronic asthma and that thromboxane receptor antagonists are unlikely to provide effective treatment for this group of patients.
Stenton
S C
SC
Chest Unit, Newcastle General Hospital, University of Newcastle upon Tyne, UK.
Young
C A
CA
Harris
A
A
Palmer
J B
JB
Hendrick
D J
DJ
Walters
E H
EH
D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000502:physiology
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D017482:Receptors, Thromboxane; D016210:Methacholine Chloride; D013928:Thromboxane A2; C060013:vapiprost