Do airway clearance mechanisms influence the local and systemic effects of inhaled corticosteroids?
The role of airway clearance in inhaled drug therapy is complex. Disease-induced bronchoconstriction results in a central drug-deposition pattern where mucociliary clearance is most efficient. When drug-induced bronchodilation is achieved, deposition and uptake becomes more peripheral, and because there is less mucociliary clearance in the periphery, this will lead to an unintentional increase in lung exposure and enhance the risk of systemic side effects. In addition, mucociliary clearance is pathologically reduced in both asthma and chronic obstructive pulmonary disease. Among inhaled corticosteroids, rate of dissolution and lung uptake differs considerably. For the slowly dissolving, lipophilic steroids, the contribution of mucociliary clearance to these findings appears significant, and variability in lung and systemic exposure resulting from variable mucociliary function appears to be amplified. In addition, dose optimisation of non-stable asthma becomes more complex. The present review highlights the impact of mucociliary clearance on inhaled corticosteroid disposition and identifies critical areas where more research is needed.
Edsbäcker
Staffan
S
AstraZeneca R&D Lund, Clinical Pharmacology, S-221 87 Lund, Sweden. Staffan.Edsbacker@astrazeneca.com
Wollmer
Per
P
Selroos
Olof
O
Borgström
Lars
L
Olsson
Bo
B
Ingelf
Jarl
J
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D016084:Bronchoconstriction; D003371:Cough / Q000503:physiopathology; D006801:Humans; D009079:Mucociliary Clearance / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000503:physiopathology
D000305:Adrenal Cortex Hormones