SELECTED ARTICLES FROM THE RECENT LITERATURE 2005

9/22/05

Delivery devices and duration of ICS therapy as factors in systemic effects

Summary
Background - Inhaled corticosteroids (ICS) are currently the preferred therapy for persistent asthma (PA). Dry powder inhalers (DPI) generate a larger particle than do current metered dose inhalers (MDI) affecting patterns of pulmonary deposition and possible systemic effects of ICS.

Findings - Whelan et al of the Asthma Clinical Research Network examined pharmacokinetics and systemic effects on the HPA axis of 2 formulations of the ICS agent fluticasone propionate (FP). FP was administered in a dose of 352 microg b.i.d. from the MDI and 400 mcg b.i.d. from a DPI. They found that FP plasma concentrations are significantly greater with MDI than with DPI administration for one week. These concentrations increased further when MDI treatment was continued for 6 weeks, suggesting that continued accumulation of FP occurs for more than one week to achieve a steady state. Linear regression analyses showed that increasing “area under the curve” for plasma FP concentrations was significantly correlated with degrees of systemic HPA suppression.

Reference
 J Allergy Clin Immunol 2005;116:525-30

Editor's Comments
These important findings are not particularly surprising. It is well recognized that more ICS are delivered to the lower respiratory tract with MDI employing the current HFA-134 propellant than occurs with DPI administration. This should lead to greater efficacy in asthma. However, because most of the systemically absorbed ICS comes from the lungs, it is not surprising that plasma FP levels were higher (and

HPA axis more suppressed) when the FP was administered by MDI. However, one would expect that asthma control could be achieved using lower doses of FP administered by MDI. The lower doses of FP should result in lower plasma FP levels, and subsequently less HPA axis suppression.

These effects are particularly prominent with use of FP, an ICS with very strong affinity for corticosteroids receptors in the airways and on target systemic tissue after absorption.

 

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