Background
Corticosteroids increase the expression of β2-adrenoceptors (β2-ARs) and protect them against down-regulation. Conversely, β2-AR agonists improve the anti-inflammatory action of corticosteroids. Nevertheless, it is still uncertain whether adding a long-acting β2-AR agonist (LABA) to an inhaled corticosteroid (ICS)
Conclusion
BDP/FF combination synergistically relaxed human bronchi; the extent of such an interaction was very strong at low-to-medium concentrations in PS small airways.
Methods
Human medium and small airways were stimulated by histamine and treated with different concentrations of BDP and FF, administered alone and in combination at concentration-ratio reproducing ex vivo that of the currently available fixed-dose combination (FDC; BDP/FF 100:6 combination-ratio). Experiments were performed in non-sensitized (NS) and passively sensitized (PS) airways. The pharmacological interaction was assessed by using Bliss Independence and Unified Theory equations.
Results
BDP/FF synergistically increased the overall bronchorelaxation in NS and PS airways (+ 15.15% ± 4.02%; P < 0.05 vs. additive effect). At low-to-medium concentrations the synergistic interaction was greater in PS than in NS bronchioles (+ 16.68% ± 3.02% and + 7.27% ± 3.05%, respectively). In PS small airways a very strong synergistic interaction (Combination Index: 0.08; + 20.04% ± 2.18% vs. additive effect) was detected for the total concentrations of BDP/FF combination corresponding to 10.6 ng/ml.
Trial registration
Not applicable.