Abstract
Assessment of adrenal suppression via systemic cortisol levels provides an indirect measure of the lung delivery of inhaled corticosteroids. This randomized, placebo-controlled, double-blind, double-dummy crossover study compared urinary and plasma cortisol levels in healthy adult volunteers following single 1,000-μg doses of budesonide from two multiple dose dry powder inhalers (DPIs). Two new formulations of budesonide (lactose and PassCal™) delivered from the Clickhaler® were compared with Pulmicort® from the Turbuhaler®. An open dose (2,000 μg) of Pulmicort Turbuhaler was included to validate the experimental model. Overnight (22:00-07:00 h) and early morning (07:00-08:00 h) urine and 08:00 h plasma samples were collected after each treatment and cortisol levels analyzed by radioimmunoassay. Combined overnight and early morning urinary cortisol values for PassCal Clickhaler and Pulmicort Turbuhaler (1,000 μg) were statistically significantly lower than placebo (p < 0.05). The lactose budesonide Clickhaler showed a non-significant urinary cortisol reduction compared with placebo. Differences between the three 1,000-μg budesonide treatments were not significant. The Pulmicort Turbuhaler 2,000 μg showed significant urinary cortisol suppression compared with placebo. Plasma cortisol showed similar effects, with significance between the two Pulmicort doses. These results suggest that adrenal suppression can be used to assess the pulmonary bioavailability of different formulation.
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