Influence of inhaler systems on systemic availability, with focus on inhaled corticosteroids

Local treatment of obstructive pulmonary diseases, such as asthma, is achieved by oral inhalation of the active substance. Drug deposited in the lung may then exert its effects locally before it is absorbed into the systemic circulation. The systemic availability of a drug is made up of the fraction deposited in the lung and the fraction deposited in the oropharynx, which is swallowed and absorbed from the gastrointestinal (GI) tract. For many drugs, the fraction absorbed from the GI-tract is subject to hepatic first-pass metabolism before reaching the systemic circulation, and for the corticosteroid budesonide, hepatic first-pass metabolism is substantial. Since metabolic inactivation of inhaled corticosteroids in the lung has not been demonstrated, the systemic absorption of the fraction deposited in the lower respiratory tract can be assumed to be proportional to lung deposition. The local versus total systemic availability (L/T-ratio) can be used to express the effectiveness of the inhaled formulation. For budesonide inhaled via a pMDI and the dry-powder inhaler, Turbuhaler, the L/T-ratio was 0.59 and 0.84, respectively. The ideal L/T-ratio is 1.0. Thus, for inhaled budesonide it is an advantage for patients to change from budesonide pMDI to budesonide Turbuhaler with respect to the balance between desired and undesired effects.