Premium
Inhibition of leukotriene D 4 ‐induced bronchoconstriction in subjects with asthma: a concentration‐effect study of ICI 204,219
Author(s) -
Smith Lewis J,
Glass Mitchell,
Minkwitz Margaret C
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.170
Subject(s) - leukotriene d4 , placebo , bronchoconstriction , antagonist , asthma , medicine , leukotriene , crossover study , pharmacology , anesthesia , receptor , alternative medicine , pathology
The peptide‐leukotriene antagonist, ICI 204,219 [4‐(5‐cyclopentyloxycarbonylamino‐lmethylindol‐3‐ylmethyl)‐3‐methoxy‐n‐o‐tolylsulfonyl benzamide], was administered 12 hours before an inhaled leukotriene D 4 (LTD 4 ) challenge during a double‐blind, placebo‐controlled, randomized, two‐period crossover trial. Subjects with mild asthma were randomized into five treatment groups (six subjects each) and received single oral doses of placebo and either 5, 10, 20, 40, or 100 mg of ICI 204,219 on day 1 of each treatment period. ICI 204,219 was tolerated well by all subjects. A progressive dose response was observed for doses of ICI 204,219 from 5 mg through 100 mg. Compared with placebo, ICI 204,219 increased the concentration (PC 20 FEV 1 ) and dose of LTD 4 needed to reduce forced expiratory volume in 1 second (FEV 1 by 20%. Mean LTD 4 PC 20 FEV 1 for groups that received placebo and 10, 40, or 100 mg ICI 204,219 increased by tenfold or more ( p< 0.05). An association was found between the plasma concentration and protective effect of ICI 204,219 ( p< 0.01). ICI 204,219 is the first leukotriene receptor antagonist for which a relationship has been established between drug plasma levels and its protective effect in subjects with asthma. Clinical Pharmacology and Therapeutics (1993) 54, 430–436; doi: 10.1038/clpt.1993.170