Pharmacodynamic and pharmacokinetic considerations in choosing an inhaled corticosteroid.

Inhaled corticosteroids are effective in controlling airway inflammation. Their anti-inflammatory effect is primarily topical, at the site of deposition in the airways. Consequently, traditional pharmacodynamic and pharmacokinetic concepts, which rely on measuring blood concentrations of drug, have limited applicability for evaluating the efficacy of topically acting inhaled corticosteroids. Important factors affecting efficacy of inhaled corticosteroids are: (i) intrinsic properties of the drugs, particularly their affinity for the corticosteroid receptor; and (ii) the newer pharmacodynamic concept of deposition characteristics of the drug formulation. Small particle formulations, especially those developed in the metered-dose inhaler with the new hydrofluoroalkane propellant, deposit to a much greater extent in the lung and may consequently have improved clinical efficacy. Lipid conjugation of inhaled corticosteroids within the lung may allow prolonged duration of effect, enabling once-daily administration. Pharmacodynamic and pharmacokinetic principles probably do not play a role in describing upper airway adverse effects occurring with inhaled corticosteroids. These are probably also determined by intrinsic properties of the drug and deposition characteristics. However, pharmacodynamic and pharmacokinetic principles seem to be important in addressing systemic safety concerns with inhaled corticosteroids. Those inhaled corticosteroids with a longer serum half-life, especially if they have higher affinity for the corticosteroid receptor, may be associated with greater systemic effects. A new pharmacokinetic concept suggests that increased protein binding within the systemic circulation and high systemic clearance of an inhaled corticosteroid may reduce the risk for systemic effects. These new pharmacodynamic and pharmacokinetic concepts provide a useful framework for identifying the characteristics of an inhaled corticosteroid with an improved benefit-to-risk profile. Increased lung deposition and reduced deposition in the upper airway should result in an inhaled corticosteroid with favorable clinical efficacy and a decreased risk for topical upper airway adverse effects. An inhaled corticosteroid with high plasma protein binding and rapid clearance might pose much less risk for systemic adverse effects than currently available drugs in this class.