Properties of the ideal corticosteroid therapy.

Currently, inhaled corticosteroids (ICSs) are the most effective long-term control therapy for persistent asthma. However, patients show a variable response to ICSs and some exhibit glucocorticoid resistance. At recommended doses, there is little evidence to suggest that ICSs can either prevent or reverse the chronic airflow limitation that develops in some asthma patients. Could an improvement in the therapeutic index and greater accessibility of the drug to peripheral airways improve patient outcomes? Can a more potent ICS overcome glucocorticoid resistance or prevent airway remodeling? An optimal response could be achieved by modifying the drug's pharmacokinetic and pharmacodynamic profile, thus maximizing potency while minimizing adverse effects, creating the "ideal" ICS. Increasing lung deposition by modifying the drug formulation, increasing the fraction of respirable particles and receptor binding affinity, and heightening lipophilicity to facilitate passage of the drug into airway cells all play a role in improving efficacy. Could a drug that undergoes lipid conjugation increase the time the drug remains in the lungs, potentially allowing for once-daily dosing? Improvements in drug safety can be achieved by optimizing half-life and plasma clearance, limiting oropharyngeal deposition by on-site activation in the lungs, and increasing plasma protein binding to reduce the amount of free drug in systemic circulation. Ciclesonide, a novel ICS currently being developed for the treatment of persistent asthma, achieves many of these positive properties. The delivery of this relatively high-potency drug to strategic areas of inflammation, without the development of significant adverse effects, ideally will lead to improved asthma outcomes.