Inhaled corticosteroids (ICS) and long-acting β 2 -agonists (LABAs) fixed dose combinations (FDCs) are widely used for the treatment of asthma while the long-acting muscarinic antagonist (LAMA) tiotropium is a standard therapy of chronic obstructive pulmonary disease (COPD). Additional improvement of lung function might be expected with the use of the triple therapy “ICS + LABA + LAMA”. The aim of this study was to assess potential synergistic bronchoprotection activity of olodaterol (LABA) combined with tiotropium (LAMA) and ciclesonide (steroid), against ovalbumin-induced bronchoconstriction in the anaesthetized guinea pig. Bronchoconstriction was induced by inhalation of a single dose of ovalbumin (50 μg/kg) and lung resistance was recorded for 10 minutes in anaesthetized guinea pigs. Compounds were given intra-tracheally 2 h before OVA challenge. Olodaterol dose-dependently inhibited the OVA-induced bronchoconstriction with an ED 50 of 0.2 μg/kg. Combination of olodaterol with either tiotropium or ciclesonide displayed bronchoprotection in a dose-dependent manner with ED 50 values 10–fold lower (0.02-0.03 μg/kg) than the ED 50 of olodaterol alone (p<0.05). The triple combination led to even better bronchoprotection with an ED 50 of 0.003 μg/kg (p<0.05). This study shows that olodaterol in combination with tiotropium and ciclesonide elicits potent synergistic bronchoprotective activity in the guinea pig. This effect is significantly higher than the summarized values of the respective monotherapies and supports the concept of the triple therapy.
Bouyssou et al. (2011) studied this question.