Combining long-acting bronchodilators with different mechanisms of action: A pharmacological approach to optimize bronchodilation of equine airways.

This research paper investigates the synergistic effect of combining two ultra long-acting bronchodilators, olodaterol and tiotropium bromide, in equine isolates, demonstrating that the blend leads to a greater degree of equine airways relaxation with a lower concentration of individual drugs, potentially reducing the risk of adverse effects.

Objective of the Study

• The primary aim of the study was to understand the interaction between the β -adrenoceptor agonist olodaterol and the muscarinic antagonist tiotropium bromide in relaxing equine airways.
• The researchers wanted to characterize the impact of combining these two drugs on equine isolated airways which were stimulated via electrical field stimulation (EFS). They used the Concentration-Reduction Index (CRI) and Combination Index (CI) equations to ascertain the synergistic or antagonistic effects of the drug combination.

Procedure and Findings

• The drugs were tested individually and in combination, reproducing the concentration-ratio delivered by the currently available fixed-dose combination (1:1).
• Both drugs alone were able to cause a significant concentration-dependent reduction in EFS-induced contractility. However, the combination of the two drugs synergistically increased this decrease in contractility, proving more potent and effective than the individual components (CI 0.18).
• The mixture of the two drugs allowed for a significant reduction in the concentration of olodaterol needed to achieve the same degree of airway relaxation.

Conclusion

• The study found that the combination of tiotropium bromide and olodaterol synergistically improves the relaxation of equine airways, thus potentially reducing the risk of adverse events when treating asthmatic horses. The combination can achieve the same level of airway muscle relaxation with lower doses of individual drugs implying its potential use for treating severe equine asthma.