Determination of lung deposition following inhalation of ciclesonide using different bioanalytical procedures

Abstract

Ciclesonide (Alvesco(®)) is an inhaled corticosteroid administered as a solution via a metered-dose inhaler, using hydrofluoroalkane HFA-134a as a propellant. Ciclesonide is inhaled as a prodrug, which is activated by pulmonary esterases to the pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC). Lung deposition is an important factor that contributes to the desired therapeutic effect of inhaled corticosteroid. More than 50% of the inhaled dose is deposited in the lung as demonstrated by scintigraphical methods after inhalation of ciclesonide. The swallowed drug does not contribute to the systemic circulation because of the low oral systemic bioavailability, which is below 1% for ciclesonide and des-CIC. Due to the negligible oral bioavailability the pharmacokinetic parameters following inhalation are a surrogate for lung deposition. The pulmonary bioavailability was more than 60% as assessed for des-CIC in pharmacokinetic studies using HPLC-MS/MS detection as bioanalytical method. Pharmacokinetics in asthmatic patients and healthy subjects are similar.