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Pharmacodynamic Evaluation of Inhaled Corticosteroids

Derendorf H.

Respiratory Drug Delivery 2014. Volume 1, 2014: 173-182.

Abstract:

There are two different purposes for quantifying the pharmacodynamic effects of inhaled corticosteroids (ICS). Systemic biomarkers such as cortisol suppression and growth retardation are adverse effects that are highly correlated to systemic corticosteroid exposure and are quantitatively predictable using appropriate pharmacokinetic/pharmacodynamic (PK/PD) models. Systemic effects may arise from ICS absorption through the lung and gastrointestinal tract. However, topical biomarkers, related presumably to ICS levels in lung target tissues, that assess therapeutic efficacy with sufficient precision to determine differences in dosage forms are still not available. Pulmonary function tests and exhaled nitrous oxide allow detection of therapeutic efficacy but lack dose-dependency. Hence, they are currently not suitable for bioequivalence testing. For regulatory purposes and determination of bioequivalence (BE), the author recommends utilizing appropriate in vitro performance parameters and measurements of systemic pharmacokinetic exposure while avoiding unnecessary, costly and uninformative clinical or insensitive pharmacodynamic studies.