Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease

M. Cazzola, S. Centanni, B. Boveri, F. Di Marco, P. Santus, M. G. Matera, L. Allegra

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: It has been suggested that the effect of a β2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. Objectives: The present study was designed to answer the question of whether combined administration of inhaled salmeterol and oral zafirlukast at the standard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. Methods: The study was performed using a double-blind, double-dummy, cross-over, randomised design, and was conducted on 4 nonconsecutive days. Sixteen patients with moderate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoker asthmatic patients received 40 mg of oral zafirlukast, 50 μg of inhaled salmeterol, 50 μg of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each patient received 400 μg of inhaled salbutamol and spirometric testing was performed 30 min later. Results: In both asthmatic and COPD patients, the overall effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p <0.0001), with a maximum bronchodilation above baseline after 180 min (20.7 and 11.0%, respectively) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subjects. Zafirlukast did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 asthmatic patients had a further improvement after the combination of salmeterol and zafirlukast. The mean difference in pre- and post-salbutamol FEV1 values in both asthmatic and COPD patients after zafirlukast was significant (p <0.05), but that after salmeterol and the combination of the two drugs was not significant (p > 10.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment. Conclusions: Both salmeterol and zafirlukast in duced a significant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinically recommended dose did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12-hour period is mandatory.

Original languageEnglish
Pages (from-to)452-459
Number of pages8
JournalRespiration
Volume68
Issue number5
DOIs
Publication statusPublished - 2001

Fingerprint

Chronic Obstructive Pulmonary Disease
Asthma
Albuterol
Forced Expiratory Volume
Therapeutics
Placebos
Leukotriene Antagonists
Airway Obstruction
zafirlukast
Salmeterol Xinafoate
Pharmaceutical Preparations
Cross-Over Studies
Lung

Keywords

  • Asthma
  • Chronic obstructive pulmonary disease
  • Combination therapy
  • Salmeterol
  • Zafirlukast

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology

Cite this

Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease. / Cazzola, M.; Centanni, S.; Boveri, B.; Di Marco, F.; Santus, P.; Matera, M. G.; Allegra, L.

In: Respiration, Vol. 68, No. 5, 2001, p. 452-459.

Research output: Contribution to journalArticle

Cazzola, M. ; Centanni, S. ; Boveri, B. ; Di Marco, F. ; Santus, P. ; Matera, M. G. ; Allegra, L. / Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease. In: Respiration. 2001 ; Vol. 68, No. 5. pp. 452-459.
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AU - Boveri, B.

AU - Di Marco, F.

AU - Santus, P.

AU - Matera, M. G.

AU - Allegra, L.

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N2 - Background: It has been suggested that the effect of a β2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. Objectives: The present study was designed to answer the question of whether combined administration of inhaled salmeterol and oral zafirlukast at the standard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. Methods: The study was performed using a double-blind, double-dummy, cross-over, randomised design, and was conducted on 4 nonconsecutive days. Sixteen patients with moderate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoker asthmatic patients received 40 mg of oral zafirlukast, 50 μg of inhaled salmeterol, 50 μg of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each patient received 400 μg of inhaled salbutamol and spirometric testing was performed 30 min later. Results: In both asthmatic and COPD patients, the overall effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p <0.0001), with a maximum bronchodilation above baseline after 180 min (20.7 and 11.0%, respectively) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subjects. Zafirlukast did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 asthmatic patients had a further improvement after the combination of salmeterol and zafirlukast. The mean difference in pre- and post-salbutamol FEV1 values in both asthmatic and COPD patients after zafirlukast was significant (p <0.05), but that after salmeterol and the combination of the two drugs was not significant (p > 10.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment. Conclusions: Both salmeterol and zafirlukast in duced a significant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinically recommended dose did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12-hour period is mandatory.

AB - Background: It has been suggested that the effect of a β2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. Objectives: The present study was designed to answer the question of whether combined administration of inhaled salmeterol and oral zafirlukast at the standard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. Methods: The study was performed using a double-blind, double-dummy, cross-over, randomised design, and was conducted on 4 nonconsecutive days. Sixteen patients with moderate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoker asthmatic patients received 40 mg of oral zafirlukast, 50 μg of inhaled salmeterol, 50 μg of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each patient received 400 μg of inhaled salbutamol and spirometric testing was performed 30 min later. Results: In both asthmatic and COPD patients, the overall effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p <0.0001), with a maximum bronchodilation above baseline after 180 min (20.7 and 11.0%, respectively) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subjects. Zafirlukast did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 asthmatic patients had a further improvement after the combination of salmeterol and zafirlukast. The mean difference in pre- and post-salbutamol FEV1 values in both asthmatic and COPD patients after zafirlukast was significant (p <0.05), but that after salmeterol and the combination of the two drugs was not significant (p > 10.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment. Conclusions: Both salmeterol and zafirlukast in duced a significant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinically recommended dose did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12-hour period is mandatory.

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KW - Chronic obstructive pulmonary disease

KW - Combination therapy

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