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Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model

G Hochhaus, H Mollmann, H Derendorf, and RJ Gonzalez-Rothi

Glucocorticoids are predominantly prescribed in asthma therapy as aerosols to achieve high pulmonary effects with reduced systemic spill-over and pronounced pulmonary selectivity. A variety of pharmacokinetic parameters are potentially important for determining pulmonary selectivity. The intent of this article, is to provide a practice-relevant theoretical approach to put the importance of these parameters on pulmonary targeting using pharmacokinetic/pharmacodynamic modeling as a tool in perspective. The applied pulmonary pharmacokinetic/pharmacodynamic model revealed that, in addition to recognized parameters such as systemic clearance, oral bioavailability, and efficiency of pulmonary deposition, other factors, such as the pulmonary release (dissolution) rate and dose, are relevant. However, the volume of distribution (for effect parameters not undergoing a diurnal rhythm) and the receptor affinity of a given glucocorticoid are not important for achieving lung targeting.
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