The effect of prior inhalation of the sulfidopeptide
leukotriene receptor antagonist,
SK&F 104353 (963 +/- 43.7 micrograms; 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 less than 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 less than 0.005). Thus, LTC4- and LTE4-induced bronchoconstrictions are both inhibited by
SK&F 104353.