A specific LTD4/LTE4-receptor antagonist improves pulmonary function in patients with mild, chronic asthma.
LY171883 is a new selective LTD4/LTE4-receptor antagonist. To evaluate the efficacy of LY171883, we studied 138 nonsmoking asthmatic patients, 18 to 65 yr old, in a double-blind, randomized block-design study. All patients were required to demonstrate a greater than or equal to 15% increase in FEV1 after inhaled bronchodilator use and were then randomly assigned to either LY171883 (600 mg) or placebo twice daily for 6 weeks. Assessment of efficacy was measured by inhaled metaproterenol use (mg/wk), symptoms, twice-daily peak expiratory flow, and weekly FEV1 measurements. LY171883-treated patients had improved FEV1 values upon completion of the treatment period compared with placebo recipients (p = 0.003). Metaproterenol use decreased in both groups, but treatment differences, though not statistically significant, favored LY171883 (p = 0.089). Of patients who used at least 23 mg/wk of metaproterenol (36 inhalations) at initiation of the study, those who received LY171883 used significantly less metaproterenol than those who received placebo (p = 0.007). LY171883 was well tolerated and reduced the need for a bronchodilator drug while improving pulmonary function. Results of this study support the hypothesis that leukotrienes LTD4 and/or LTE4 may be important in the pathogenesis of asthma in humans.
Cloud
M L
ML
Indiana University, Indianapolis.
Enas
G C
GC
Kemp
J
J
Platts-Mills
T
T
Altman
L C
LC
Townley
R
R
Tinkelman
D
D
King
T
T
Middleton
E
E
Sheffer
A L
AL
D000098:Acetophenones; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D055598:Chemical Phenomena; D002621:Chemistry; D002908:Chronic Disease; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009921:Metaproterenol / Q000627:therapeutic use; D015337:Multicenter Studies as Topic; D011897:Random Allocation; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000037:antagonists & inhibitors; D013777:Tetrazoles
D000098:Acetophenones; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; D013777:Tetrazoles; D009921:Metaproterenol; C044660:LY 171883