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A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy.
Ann Allergy Asthma Immunol. 1998 Jul; 81(1):43-9.AA

Abstract

BACKGROUND

Previous studies demonstrated that leukotriene receptor antagonists (LTRAs) are effective in reducing asthma symptoms and the airway response to inhaled leukotriene D4 (LTD4) in asthmatic patients receiving inhaled beta2-agonists alone.

OBJECTIVE

To investigate the efficacy of a single 20-mg dose of the oral LTRA zafirlukast in reducing the airway response to inhaled LTD4 in mild-to-moderate asthmatic patients receiving inhaled beta2-agonists and inhaled corticosteroids (ICS).

METHODS

In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 microg/day; range 336 to 1600 microg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 microg/mL LTD4, received either zafirlukast or placebo on each of two study days. Two hours after dosing, patients underwent bronchoprovocation challenges with increasing concentrations of LTD4 (0.1 to 1000 microg/mL) at 10-minute intervals until either the patient's FEV1 decreased by 20% or the maximum concentration of LTD4 was given. Spirometric tests were done just before (baseline) and throughout the challenge phase until the patient's FEV1 returned to within 5% of baseline. Blood samples were collected two hours after dosing to determine plasma concentrations of zafirlukast.

RESULTS

Compared with placebo, zafirlukast produced a 1.82-unit increase in logPC20FEV1 and a 1.88-unit increase in logPD20FEV1, representing a 66-fold higher concentration and a 76-fold higher dose of LTD4, respectively, to produce a 20% decrease in FEV1 (P < .001). Mean time to recovery after challenge was 36.7 versus 51.7 minutes when patients received zafirlukast and placebo, respectively. No correlation between clinical effects and plasma drug levels was observed.

CONCLUSIONS

This trial demonstrated that asthmatic patients on maintenance ICS can respond to exogenously administered LTD4 and that zafirlukast reduced the airway response to LTD4 in these patients.

Authors+Show Affiliations

Northwestern University, Chicago, Illinois, USA.No affiliation info availableNo 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

9690572

Citation

Smith, L J., et al. "A Single Dose of Zafirlukast Reduces LTD4-induced Bronchoconstriction in Patients On Maintenance Inhaled Corticosteroid Therapy." Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, vol. 81, no. 1, 1998, pp. 43-9.
Smith LJ, Hanby LA, Lavins BJ, et al. A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy. Ann Allergy Asthma Immunol. 1998;81(1):43-9.
Smith, L. J., Hanby, L. A., Lavins, B. J., & Simonson, S. G. (1998). A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy. Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, 81(1), 43-9.
Smith LJ, et al. A Single Dose of Zafirlukast Reduces LTD4-induced Bronchoconstriction in Patients On Maintenance Inhaled Corticosteroid Therapy. Ann Allergy Asthma Immunol. 1998;81(1):43-9. PubMed PMID: 9690572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy. AU - Smith,L J, AU - Hanby,L A, AU - Lavins,B J, AU - Simonson,S G, PY - 1998/8/5/pubmed PY - 1998/8/5/medline PY - 1998/8/5/entrez SP - 43 EP - 9 JF - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology JO - Ann Allergy Asthma Immunol VL - 81 IS - 1 N2 - BACKGROUND: Previous studies demonstrated that leukotriene receptor antagonists (LTRAs) are effective in reducing asthma symptoms and the airway response to inhaled leukotriene D4 (LTD4) in asthmatic patients receiving inhaled beta2-agonists alone. OBJECTIVE: To investigate the efficacy of a single 20-mg dose of the oral LTRA zafirlukast in reducing the airway response to inhaled LTD4 in mild-to-moderate asthmatic patients receiving inhaled beta2-agonists and inhaled corticosteroids (ICS). METHODS: In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 microg/day; range 336 to 1600 microg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 microg/mL LTD4, received either zafirlukast or placebo on each of two study days. Two hours after dosing, patients underwent bronchoprovocation challenges with increasing concentrations of LTD4 (0.1 to 1000 microg/mL) at 10-minute intervals until either the patient's FEV1 decreased by 20% or the maximum concentration of LTD4 was given. Spirometric tests were done just before (baseline) and throughout the challenge phase until the patient's FEV1 returned to within 5% of baseline. Blood samples were collected two hours after dosing to determine plasma concentrations of zafirlukast. RESULTS: Compared with placebo, zafirlukast produced a 1.82-unit increase in logPC20FEV1 and a 1.88-unit increase in logPD20FEV1, representing a 66-fold higher concentration and a 76-fold higher dose of LTD4, respectively, to produce a 20% decrease in FEV1 (P < .001). Mean time to recovery after challenge was 36.7 versus 51.7 minutes when patients received zafirlukast and placebo, respectively. No correlation between clinical effects and plasma drug levels was observed. CONCLUSIONS: This trial demonstrated that asthmatic patients on maintenance ICS can respond to exogenously administered LTD4 and that zafirlukast reduced the airway response to LTD4 in these patients. SN - 1081-1206 UR - https://www.unboundmedicine.com/medline/citation/9690572/A_single_dose_of_zafirlukast_reduces_LTD4_induced_bronchoconstriction_in_patients_on_maintenance_inhaled_corticosteroid_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1081-1206(10)63108-0 DB - PRIME DP - Unbound Medicine ER -