Comparative effects of a fixed combination of reproterol hydrochloride and disodium cromoglycate with each agent alone on antigen-induced airway responses in sheep.

Abstract

The purpose of this study was to compare the effectiveness of an eight day treatment with clinically relevant doses of a fixed combination of the beta 2 mimetic reproterol hydrochloride and disodium cromoglycate with each agent given alone against antigen-induced early (EAR) and late airway responses (LAR) as well as post-antigen-induced airway hyperresponsiveness (AHR) in allergic sheep. Animals were treated in a randomized fashion with either the inhaled combination (n = 6), reproterol hydrochloride alone (n = 6), disodium cromoglycate alone (n = 6), or placebo (n = 8). Treatments (two puffs from a metered dose inhaler) were given three times a day for 7 days and once on the 8th day 1 h before airway challenge with Ascaris suum antigen. In the placebo trial, antigen challenge resulted in EAR and LAR as measured by increases in specific lung resistance; these changes were followed 24h later by AHR to inhaled carbachol. With respect to the placebo trial, treatment with reproterol hydrochloride reduced the EAR (P < 0.05) and blocked the LAR (P < 0.05), but had no effect on the post-challenge AHR. Treatment with disodium cromoglycate also reduced the EAR (P < 0.05), blocked the LAR (P < 0.05), and blocked the post-antigen-induced AHR (P < 0.05). Treatment with the fixed combination reduced the EAR (P < 0.05), blocked the LAR (P < 0.05), and blocked the post-antigen-induced AHR (P < 0.05). Comparison of the different agents indicated that the fixed combination gave significantly increased protection against the EAR than either agent alone, gave slightly better (P < 0.05) protection against the late response than cromolyn sodium and gave better protection against post-antigen-induced AHR than reproterol hydrochloride alone. These results suggest that a fixed combination of a beta 2-mimetic and disodium cromoglycate provides some increased protection against antigen-induced airway responses when compared to either agent alone in a controlled laboratory setting.

• Authors: W M Abraham, J R Sabater, S Szelenyi, M Bähre
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 11 Issue 4 Pg. 271-6 ( 1998) ISSN: 1094-5539 [Print] England
• PMID: 10101743 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic beta-Agonists
• Aerosols
• Anti-Allergic Agents
• Bronchodilator Agents
• Drug Combinations
• reproterol
• Metaproterenol
• Theophylline
• Cromolyn Sodium

Topics

• Administration, Inhalation
• Adrenergic beta-Agonists (pharmacology, therapeutic use)
• Aerosols
• Airway Resistance (drug effects)
• Animals
• Anti-Allergic Agents (pharmacology, therapeutic use)
• Area Under Curve
• Asthma (drug therapy, physiopathology)
• Bronchial Hyperreactivity (physiopathology, prevention & control)
• Bronchial Provocation Tests
• Bronchodilator Agents (pharmacology, therapeutic use)
• Cromolyn Sodium (pharmacology, therapeutic use)
• Drug Combinations
• Drug Therapy, Combination
• Metaproterenol (analogs & derivatives, pharmacology, therapeutic use)
• Random Allocation
• Sheep
• Theophylline (analogs & derivatives, pharmacology, therapeutic use)