BAY u3405, a thromboxane A2 antagonist, reduces bronchial hyperresponsiveness in asthmatics.

OBJECTIVE Thromboxane A2 (TXA2) is reported to induce bronchial hyperresponsiveness along with the well-documented bronchoconstrictor action on smooth muscles. We examined the effect of the TXA2 antagonist, BAY u3405, on bronchial hyperresponsiveness to methacholine (MCh) in asthmatics. PATIENTS Twelve adult asthmatics were studied in a randomized, double-blind, placebo-controlled, crossover fashion. DESIGN Following a 2-week run-in period, the subjects were administered 75 mg of BAY u3405 or placebo orally, twice a day for 2 weeks each in a crossover design, interposing a 2-week washout period. Bronchial hyperresponsiveness was measured by the astograph method. Briefly, the respiratory resistance (Rrs) was measured by the forced oscillation method during continuous inhalation of MCh in stepwise incremental concentrations, until Rrs reached twice the baseline value. Bronchial hyperresponsiveness was evaluated as the minimum cumulative dose (Dmin) of MCh that induced an increase in Rrs. Dmin was calculated so that 1 U of Dmin equals to 1 min of inhalation of aerosol solution at 1.0 mg/mL during quiet breathing. RESULTS Three subjects were withdrawn from the evaluation because they had asthmatic attacks or wheezing during the study. The Dmin value of 0.533 U (GSEM 1.675) after the BAY u3405 treatment was significantly greater than that of 0.135 U (GSEM 1.969) after the placebo treatment (p = 0.0139). There were no safety concerns in either treatment group. CONCLUSION We conclude that BAY u3405 may be a useful drug for attenuating bronchial hyperresponsiveness in bronchial asthma.

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