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

¹ From the Second Department of Internal Medicine, Sasebo City General Hospital, Nagasaki, Japan
² From the Nagasaki University School of Medicine, and the Department of Internal Medicine, Sasebo City General Hospital, Nagasaki, Japan

Yasushi Obase, MD, The Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto-machi, Nagasaki 852-8501, Japan; e-mail: obadann-ngs{at}umin.u-tokyo.ac.jp

Background: Leukotriene (LT) and thromboxane A₂ (TXA₂) receptor antagonists have been used in the treatment of asthma.

Objectives: We examined the effects of an LT receptor antagonist, TXA₂ receptor antagonist, and TXA₂ 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), TXA₂ receptor antagonist (seratrodast, 80 mg/d), or TXA₂ synthetase inhibitor (ozagrel, 800 mg/d) was administered orally over 7 days at random using a cross-over method (BPT2-4). Blood levels of LTB₄, LTC₄, LTD₄, 11-dehydrothromboxane B₂, 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 < 0.0001) and LAR by 54.6% (p = 0.0391). Ozagrel significantly suppressed IAR by 39.5% (p = 0.0413), but the fall in FEV₁ 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 TXA₂. Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma.

Key Words: antigen-induced bronchoconstriction • chemical mediators • cysteinyl-leukotriene receptor antagonist • thromboxane A₂ receptor antagonist • thromboxane A₂ synthetase inhibitor

Submitted on October 17, 1997
Accepted on May 11, 1998

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