TY - JOUR
T1 - A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy
AU - Smith, Lewis J.
AU - Hanby, Laura A.
AU - Lavins, Bernard J.
AU - Simonson, Steven G.
N1 - Funding Information:
This research was supported by a grant from Zeneca Pharmaceuticals, Wilmington, Delaware. Received for publication February 13, 1998. Accepted for publication in revised form May 11, 1998.
PY - 1998/7
Y1 - 1998/7
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 β2-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 β2-agonists and inhaled corticosteroids (ICS). Methods: In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 μg/day; range 336 to 1600 μg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 μg/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 μg/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.
AB - 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 β2-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 β2-agonists and inhaled corticosteroids (ICS). Methods: In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 μg/day; range 336 to 1600 μg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 μg/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 μg/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.
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U2 - 10.1016/S1081-1206(10)63108-0
DO - 10.1016/S1081-1206(10)63108-0
M3 - Article
C2 - 9690572
AN - SCOPUS:0031820252
SN - 1081-1206
VL - 81
SP - 43
EP - 49
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 1
ER -