A pilot study comparing the antispasmodic effects of inhaled salmeterol, salbutamol and ipratropium bromide using different aerosol devices on muscarinic bronchoconstriction in healthy cats

Abstract

This study compared the duration and magnitude of the antispasmodic effects of salmeterol (SLM), salbutamol (SAL), ipratropium bromide (IB) and the combination of SAL and IB (SAL/IB) against carbachol-induced bronchoconstriction in healthy cats, and investigated the gain in efficacy using a two or fourfold increase in drug dosages. The drug regimens used were: (1) SLM 25 μg, SAL 100 μg, IB 20 μg and SAL/IB 100 μg/20 μg for bronchodilators delivered by a metered-dose inhaler (MDI); (2) SAL 3.75 mg and IB 62.5 μg for nebulised (NEB) medications. To monitor the bronchodilator effect, airway responsiveness was assessed at different time points using barometric whole-body plethysmography and calculation of the concentration of inhaled carbachol inducing a 300% increase of baseline Penh (enhanced pause), an estimator of airflow limitation. Maximum C-Penh300 was recorded 15 min after NEB SAL, IB MDI, NEB IB and 1 h after SAL MDI and 4 h after SLM MDI, respectively. C-Penh300 was significantly different from control values (without treatment) up to 24 h for SLM MDI, 8 h for IB MDI and 4 h for other drugs. In terms of efficacy, SAL/IB MDI showed a synergistic antispasmodic effect at 15 min, 4 h and 8 h after administration. A fourfold increase of the initial dose of IB MDI and NEB IB significantly increased C-Penh300. Despite a fourfold dose increase, SLM displayed the weakest degree of bronchoprotection compared to other bronchodilators. The study provides evidence that inhaled bronchodilators are efficient at preventing muscarinic-induced bronchospasm in healthy cats and that SAL and IB appear to be short-acting bronchodilators in contrast to SLM.