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Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI 204,219.
Clin Pharmacol Ther. 1993 Oct; 54(4):430-6.CP

Abstract

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 D4 (LTD4) 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 (PC20FEV1) and dose of LTD4 needed to reduce forced expiratory volume in 1 second (FEV1) by 20%. Mean LTD4 PC20FEV1 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.

Authors+Show Affiliations

Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8222486

Citation

Smith, L J., et al. "Inhibition of Leukotriene D4-induced Bronchoconstriction in Subjects With Asthma: a Concentration-effect Study of ICI 204,219." Clinical Pharmacology and Therapeutics, vol. 54, no. 4, 1993, pp. 430-6.
Smith LJ, Glass M, Minkwitz MC. Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI 204,219. Clin Pharmacol Ther. 1993;54(4):430-6.
Smith, L. J., Glass, M., & Minkwitz, M. C. (1993). Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI 204,219. Clinical Pharmacology and Therapeutics, 54(4), 430-6.
Smith LJ, Glass M, Minkwitz MC. Inhibition of Leukotriene D4-induced Bronchoconstriction in Subjects With Asthma: a Concentration-effect Study of ICI 204,219. Clin Pharmacol Ther. 1993;54(4):430-6. PubMed PMID: 8222486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI 204,219. AU - Smith,L J, AU - Glass,M, AU - Minkwitz,M C, PY - 1993/10/1/pubmed PY - 1993/10/1/medline PY - 1993/10/1/entrez SP - 430 EP - 6 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 54 IS - 4 N2 - 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 D4 (LTD4) 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 (PC20FEV1) and dose of LTD4 needed to reduce forced expiratory volume in 1 second (FEV1) by 20%. Mean LTD4 PC20FEV1 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. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/8222486/Inhibition_of_leukotriene_D4_induced_bronchoconstriction_in_subjects_with_asthma:_a_concentration_effect_study_of_ICI_204219_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0009-9236&amp;date=1993&amp;volume=54&amp;issue=4&amp;spage=430 DB - PRIME DP - Unbound Medicine ER -