Inhalation safety and tolerability of a novel fixed-dose combination of glycopyrronium-vilanterol powder in Wistar rats.

Fixed-dose combinations (FDCs) offer therapeutic benefits like enhanced efficacy, reduced adverse effects, and better patient compliance, making them cost-effective. They are particularly effective in managing chronic obstructive pulmonary disease (COPD). Combining a long-acting muscarinic antagonist with a long-acting beta-agonist improves lung function, reduces the need for rescue bronchodilators, alleviates respiratory symptoms, and enhances the overall quality of life in COPD patients. This study evaluated the safety and tolerability of a novel FDC containing vilanterol, a selective β2-adrenoreceptor agonist, and glycopyrronium, an antimuscarinic agent, in Wistar rats. Vilanterol promotes bronchodilation, while glycopyrronium reduces bronchoconstriction. Repeated-dose toxicity testing at three dosage levels (6.25 + 12.5 mcg/kg/day, 12.5 + 25 mcg/kg/day, and 25 + 50 mcg/kg/day) through nose-only exposure showed that the FDC was well-tolerated, with no significant clinical signs of toxicity. Key parameters, including body weight, feed consumption, ophthalmic examination, clinical pathology, and bronchoalveolar lavage fluid analysis, showed no adverse effects. Minimal, non-dose-related microscopic lesions and normal alveolar macrophage responses were observed. The no-observed-adverse-effect level, based on actual concentration and duration of exposure, was established at 25 + 50 mcg/kg/day, indicating the FDC's safety and suitability for further development in COPD management.