The effect of inhalation of the leukotriene receptor antagonist, SK&F 104353, on leukotriene C 4- and leukotriene E 4-induced bronchoconstriction in subjects with asthma

Abstract

The effect of prior inhalation of the sulfidopeptide leukotriene receptor antagonist, SK&F 104353 (963 ± 43.7 μg; mean ± SEM), on (LTC 4)- and leukotriene E 4 (LTE 4)-induced bronchoconstriction has been studied in six subjects with asthma (six male subjects, aged 24 to 36 years). Inhalation challenges with either synthetic LTC 4 or LTE 4 were performed after prior inhalation of aerosolized SK&F 104353 or placebo in a double-blind, randomized fashion. Airway responsiveness to each agonist was determined by the cumulative dose of agonist required to induce a 35% fall in specific airway conductance (PD 35) as determined by linear interpolation of the log dose-response curve. There was no change in baseline specific airway conductance after inhalation of either placebo or SK&F 104353. LTC 4- and LTE 4-induced bronchoconstrictions were significantly inhibited by aerosolized inhalation of SK&F 104353 30 minutes before challenge. The geometric mean (GM) PD 35 of LTC 4 on the open-therapy and placebo-therapy days was 0.043 nmol (range, 0.01 to 0.1 nmol) and 0.036 nmol (range, 0.01 to 0.1 nmol), respectively. On the treatment day with SK&F 104353, it was not possible to obtain a GM PD 35 LTC 4 up to a maximum concentration of 0.52 nmol LTC 4 ( p < 0.01). The GM PD 35 of LTE 4 on the open-therapy and placebo-therapy days was 0.30 nmol (range, 0.13 to 0.76 nmol) and 0.39 nmol (range, 0.14 to 0.9 nmol), respectively. On the treatment day with SK&F 104353, it was not possible to obtain a GM PD 35 LTE 4 up to a maximum concentration of 5 nmol LTE 4 ( p < 0.005). Thus, LTC 4- and LTE 4-induced bronchoconstrictions are both inhibited by SK&F 104353.