Effect of the oral leukotriene D4 antagonist LY171883 on inhaled and intradermal challenge with antigen and leukotriene D4 in atopic subjects.
Sulfidopeptide leukotrienes have been suggested as potential mediators of the bronchoconstriction of asthma. The effect of the orally active leukotriene D4 (LTD4) antagonist LY171883 (LY) (400 mg) on antigen or LTD4-induced bronchoconstriction and wheal-and-flare responses was studied in atopic subjects on six occasions (three groups of 2 consecutive days). On the first 2 study days, subjects were screened for their response to inhaled LTD4 and antigen. On the second and third groups of 2 study days, subjects received LY, 400 mg, or placebo 2 hours before inhaled leukotriene LTD4 or antigen challenge. After antigen challenge, the lung function was measured for 6 hours. After the inhaled challenge, intradermal LTD4 and antigen challenges were performed. LY had no effect on baseline lung function. Geometric mean (95% confidence intervals) for the provocative dose of LTD4 causing a 40% fall in forced expiratory flow at 40% vital capacity from a forced expiratory flow maneuver was 1.8 (0.5 to 5.6) nmol after placebo and 5.6 (2.0 to 15.7) nmol after LY. This difference was not significant. The mean maximum change during the early phase of antigen-induced bronchoconstriction was reduced, being 54.7 (26.9% to 82.4%) after placebo and 35.8 (2.3% to 69.3%) after LY (p less than 0.05). There was, however, no difference in the maximum response observed during the late phase. There was also a significant reduction in the area under the curve of the early but not late-phase response to antigen. LY significantly shifted the intradermal LTD4 dose-response curve for both wheal and flare to the right (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Fuller
R W
RW
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, England.
Black
P N
PN
Dollery
C T
CT
D000098:Acetophenones / Q000494:pharmacology*; D000280:Administration, Inhalation; D000328:Adult; D000941:Antigens / Q000008:administration & dosage; D001393:Azoles / Q000494:pharmacology*; D006801:Humans; D007428:Intradermal Tests; D008297:Male; D013189:SRS-A / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000494:pharmacology*
D000098:Acetophenones; D000941:Antigens; D001393:Azoles; D013189:SRS-A; D013777:Tetrazoles; C044660:LY 171883