THE EFFECT OF INHALATION OF THE LEUKOTRIENE RECEPTOR ANTAGONIST, SK-AND-F 104353, ON LEUKOTRIENE C4-INDUCED 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-mu-g; 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.