Pharmaceutical characteristics that influence the clinical efficacy of inhaled corticosteroids

Inhaled corticosteroids (ICSs) are the most effective therapy for the management of persistent asthma. The aim of ICS therapy is to achieve a high anti-inflammatory effect in the airways with a concomitant low risk of unwanted local and systemic effects. Direct estimates of clinical efficacy and potency based on studies in humans are difficult to interpret.

To examine the challenges of using alternative estimates of ICS efficacy and potency, including pharmaceutical characteristics.

Articles published from 1990 to 2002 on the potency, efficacy, and tolerability of ICSs were identified using MEDLINE and in-house databases and were then reviewed. Search terms included inhaled corticosteroid, budesonide, fluticasone, beclomethasone, mometasone, and potency.

Differences among ICSs can be readily shown using preclinical measures, such as glucocorticoid receptor binding or skin blanching tests. However, pharmaceutical (delivery and pharmacokinetic) differences of ICSs can have a greater impact on clinical efficacy than in vitro potency differences. For example, the unique esterification of budesonide in the airways prolongs its local activity and may contribute positively to its efficacy and therapeutic index. Although comparative clinical trials suggest 6-fold differences in potencies among ICSs, there is currently no evidence to support differences in efficacy when they are administered at equipotent dosages.

Greater preclinical potency of an ICS does not imply greater clinical efficacy. Pharmacokinetic factors can have a significant impact on relative clinical efficacy.