Effects of Cysteinyl-Leukotriene Receptor Antagonist, Thromboxane A2 Receptor Antagonist, and Thromboxane A2 Synthetase Inhibitor on Antigen-Induced Bronchoconstriction in Patients With Asthma

Background Leukotriene (LT) and thromboxane A 2 (TXA 2 ) receptor antagonists have been used in the treatment of asthma. Objectives : We examined the effects of an LT receptor antagonist, TXA 2 receptor antagonist, and TXA 2 synthetase inhibitor on bronchoprovocation test (BPT) in patients with mild-to-moderate atopic asthma. Methods BPT was performed four times in each of six asthmatics. Development of the immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) was confirmed on the first BPT (BPT1). After a 7-day washout period, an LT receptor antagonist (pranlukast, 450 mg/d), TXA 2 receptor antagonist (seratrodast, 80 mg/d), or TXA 2 synthetase inhibitor (ozagrel, 800 mg/d) was administered orally over 7 days at random using a cross-over method (BPT2-4). Blood levels of LTB 4 , LTC 4 , LTD 4 , 11-dehydrothromboxane B 2 , eosinophil cationic protein, and histamine were measured at reaction phases of pre-BPT, IAR, and LAR. Results Administration of pranlukast suppressed IAR by 80.5% (p 1 was >20% (21.56 ± 4.173%). Seratrodast did not suppress IAR or LAR. Blood levels of chemical mediators did not correlate with the suppressive effects of the tested drugs. Conclusions The LT receptor antagonist was considered to be the most effective. LT might play a more important role in the pathogenesis of asthma than TXA 2 . Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma.