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.
BACKGROUND
It has been suggested that the effect of a beta2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist.


OBJECTIVE
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, crossover, randomised design, and was conducted on 4 non-consecutive 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 microg of inhaled salmeterol, 50 microg 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 microg 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 > 0.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment.


CONCLUSIONS
Both salmeterol and zafirlukast induced 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.
Cazzola
M
M
Division of Pneumology and Allergology and Unit of Respiratory Clinical Pharmacology, A. Cardarelli Hospital, Naples, Italy. mcazzola@qubisoft.it
Centanni
S
S
Boveri
B
B
Di Marco
F
F
Santus
P
P
Matera
M G
MG
Allegra
L
L
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000819:agonists* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents / Q000819:agonists* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D000068299:Salmeterol Xinafoate; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D000068299:Salmeterol Xinafoate; D000420:Albuterol; C062735:zafirlukast