BAY U3405, A THROMBOXANE A(2) ANTAGONIST, REDUCES BRONCHIAL HYPERRESPONSIVENESS IN ASTHMATICS

Objectives: Thromboxane A(2) (TXA(2)) is reported to induce bronchial hyperresponsiveness along with the well-documented bronchoconstrictor action on smooth muscles. We examined the effect of the TXA(2) antagon ist, BAY u3405, on bronchial hyperresponsiveness to methacholine (MCh) in asthmatics. Patients: Twelve adult asthmatics were studied in a ra ndomized, double-blind, placebo-controlled, crossover fashion. Design: Following a 2-week run-in period, the subjects were administered 75 m g of BAY u3405 or placebo orally, twice a day for 2 weeks each in a cr ossover design, interposing a 2-week washout period. Bronchial hyperre sponsiveness was measured by the astograph method. Briefly, the respir atory resistance (Brs) was measured by the forced oscillation method d uring continuous inhalation of MCh in stepwise incremental concentrati ons, until Rrs reached twice the baseline value. Bronchial hyperrrespo nsiveness was evaluated as the minimum cumulative dose (Dmin) of MCh t hat induced an increase in Rrs. Dmin was calculated so that 1 U of Dmi n equals to 1 min of inhalation of aerosol solution at 1.0 mg/mL durin g quiet breathing. Results: Three subjects were withdrawn from the eva luation because they had asthmatic attacks or wheezing during the stud y. The Dmin value of 0.533 U (GSEM 1.675) after the BAY u3405 treatmen t was significantly greater than that of 0.135 U (GSEM 1.969) after th e placebo treatment (p=0.0139). There were no safety concerns in eithe r treatment group. Conclusion: We conclude that BAY u3405 may be a use ful drug for attenuating bronchial hyperresponsiveness in bronchial as thma.