The Lack of Bronchodilator Effect and the Short-term Safety of Cumulative Single Doses of an Inhaled Potassium Channel Opener (Bimakalim) in Adult Patients with Mild to Moderate Bronchial Asthma

Abstract

Summary: The aim of this study was to assess the bronchodilator effect and short-term safety of cumulative single doses of inhaled bimakalim (E Merck, Darmstadt), a potassium channel opener, compared to placebo in 12 adult patients with chronic, mild to moderate, non-allergic bronchial asthma. The study was a randomized, placebo-controlled, cross-over study and the only efficacy variable measured was the forced expiratory volume in one second (FEV 1). The patients had an FEV -1 >50% of predicted normal value and a reversibility of more than 15% at entrance to the study. Inhaled bimakalim and placebo were delivered by a Pariboy nebulizer. The doses tested in a cumulative manner were 10, 25, 40 and 100 μg (total cumulative dose 175 μg), each individual dose given at 60-min intervals. Plasma bimakalim concentrations were measured at time 0 and 60 min after each dose. No bronchodilator effect was shown, with inhaled bimakalim at the doses tested. Reasons for the lack of efficacy of inhaled bimakalim in this study may be due to low doses of administrated drug or to a true lack of bronchodilatation effect in the study patients. Inhaled bimakalim was well tolerated. No headache or cardiovascular events were seen with the cumulative dose of 175 μg bimakalim.