The effect of inhalation of the leukotriene receptor antagonist, SK&F 104353, on leukotriene C₄- and leukotriene E₄-induced bronchoconstriction in subjects with asthma

The effect of prior inhalation of the sulfidopeptide leukotriene receptor antagonist, SK&F 104353 (963 ± 43.7 μg; mean ± SEM), on (LTC₄)- and leukotriene E₄ (LTE₄)-induced bronchoconstriction has been studied in six subjects with asthma (six male subjects, aged 24 to 36 years). Inhalation challenges with either synthetic LTC₄ or LTE₄ 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 (PD₃₅) 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. LTC₄- and LTE₄-induced bronchoconstrictions were significantly inhibited by aerosolized inhalation of SK&F 104353 30 minutes before challenge. The geometric mean (GM) PD₃₅ of LTC₄ 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 PD₃₅ LTC₄ up to a maximum concentration of 0.52 nmol LTC₄ (p < 0.01). The GM PD₃₅ of LTE₄ 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 PD₃₅ LTE₄ up to a maximum concentration of 5 nmol LTE₄ (p < 0.005). Thus, LTC₄- and LTE₄-induced bronchoconstrictions are both inhibited by SK&F 104353.