Effects of SK&F 104353, a leukotriene receptor antagonist, on the bronchial responses to histamine in subjects with asthma: A comparative study with terfenadine

Abstract

We compared the effects of pretreatment of 800 μg of inhaled Smith Kline & French (SK&F) 104353, a leukotriene receptor antagonist, and 120 mg of oral terfenadine on the bronchial responses to inhaled histamine in 12 subjects with asthma. The study took place on 3 different days and was conducted according to a double-blind, crossover, double-dummy, randomized, and placebo-controlled design. There was no difference in baseline and prechallenge FEV 1 after placebo, SK&F 104353, and terfenadine administration. The median ratio of the provocative dose causing a 20% fall in FEV 1 from baseline (PD 20) with terfenadine over PD 20 with placebo was 12.36 (range, 3.2 to 30.3; p < 0.01) and that of PD 20 with SK&F 104353 over PD 20 with placebo was 1.51 (range, 0.8 to 5.9; not significant). Analysis of individual results demonstrated a shift toward the right of the dose-response curves to histamine with SK&F 104353 compared to that with placebo in three subjects, whereas the active compound did not exhibit any protective effect against histamine in the remaining nine subjects. We conclude that there is a leukotriene component to the bronchial responses to histamine in some, but not all, subjects. This component remains, however, small and does not appear to be clinically important in the population of subjects with asthma that was studied.