Evaluation of Pulmonary Absorption Using Pharmacokinetic Methods

Abstract

When assessing inhaled drug absorption, standard pharmacokinetic analyses cannot differentiate drug that reaches the systemic circulation from the lungs from that of the gut. Pulmonary absorption kinetics can be assessed for drugs with negligible gastrointestinal absorption or for drugs that are eliminated via first-pass metabolism. For other drugs, pulmonary absorption kinetics can be studied by blocking gastrointestinal absorption with charcoal, or by studying absorption during the first 30 minutes post inhalation before appreciable oral absorption has occurred. Pharmacokinetic data generally agree well with pulmonary deposition data derived by measuring inhaled radiotracer-labelled drug using γ-scintigraphy. Monitoring pulmonary and oral absorption also provides information on total systemic exposure and therefore safety. Furthermore, the duration of action of different inhaled drugs and the degree of pulmonary targeting can be obtained by determining the corticosteroid occupancy of lung and systemic glucocorticoid receptors. Pharmacokinetic data from healthy volunteers cannot be extrapolated to patients with asthma, as systemic exposure to inhaled drugs can be markedly less in patients than in healthy volunteers. This correlates with the observed differences in side effects in these two groups. Although pharmacokinetic methods do not provide information on regional deposition, they do generate data on systemic and pulmonary exposure, and so play a role in the development of delivery systems.