The following observations relevant to systemic absorption were made in clinical studies. In one uncontrolled study a statistically significant decrease in responsiveness to metyrapone was noted in 15 adult steroid-independent patients treated with mg of flunisolide per day (the maximum recommended dose) for 3 months. A small but statistically significant drop in eosinophils from % to % of total circulating leucocytes was noted in another study in children who were not taking oral corticosteroids simultaneously. A 5% incidence of menstrual disturbances was reported during open studies, in which there were no control groups for comparison.
Studies with oral and intravenous dosing of radiolabeled ciclesonide have shown an incomplete extent of oral absorption (%). The oral bioavailability of both ciclesonide and the active metabolite is negligible (<% for ciclesonide, <1% for the metabolite). Based on a γ-scintigraphy experiment, lung deposition in healthy subjects is 52%. In line with this figure, the systemic bioavailability for the active metabolite is >50% by using the ciclesonide metered dose inhaler. As the oral bioavailability for the active metabolite is <1%, the swallowed portion of the inhaled ciclesonide does not contribute to systemic absorption.