Effects of SK&F 104353, a leukotriene receptor antagonist, on the bronchial responses to histamine in subjects with asthma: a comparative study with terfenadine.
We compared the effects of pretreatment of 800 micrograms of inhaled Smith Kline & French (SK&F) 104353, a leukotriene receptor antagonist, and 120 mg of oral terfenadine on the bronchial responses to inhaled histamine in 12 subjects with asthma. The study took place on 3 different days and was conducted according to a double-blind, crossover, double-dummy, randomized, and placebo-controlled design. There was no difference in baseline and prechallenge FEV1 after placebo, SK&F 104353, and terfenadine administration. The median ratio of the provocative dose causing a 20% fall in FEV1 from baseline (PD20) with terfenadine over PD20 with placebo was 12.36 (range, 3.2 to 30.3; p less than 0.01) and that of PD20 with SK&F 104353 over PD20 with placebo was 1.51 (range, 0.8 to 5.9; not significant). Analysis of individual results demonstrated a shift toward the right of the dose-response curves to histamine with SK&F 104353 compared to that with placebo in three subjects, whereas the active compound did not exhibit any protective effect against histamine in the remaining nine subjects. We conclude that there is a leukotriene component to the bronchial responses to histamine in some, but not all, subjects. This component remains, however, small and does not appear to be clinically important in the population of subjects with asthma that was studied.
Dinh Xuan
A T
AT
Département des Maladies Respiratoires, Hôpital Cochin, Paris, France.
Regnard
J
J
Similowski
T
T
Rey
J
J
Marsac
J
J
Lockhart
A
A
D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D002986:Clinical Trials as Topic; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D013189:SRS-A / Q000037:antagonists & inhibitors*; D016593:Terfenadine
D001559:Benzhydryl Compounds; D003998:Dicarboxylic Acids; D006634:Histamine H1 Antagonists; D013189:SRS-A; D016593:Terfenadine; D006632:Histamine; C052393:pobilukast