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Increasing affinity to lung tissue is an important strategy to achieve pulmonary retention and to prolong the duration of effect in the lung. As the lung is a very heterogeneous organ, differences in structure and blood flow may influence local pulmonary disposition. Here, a novel lung preparation technique was employed to investigate regional lung distribution of four drugs (salmeterol, fluticasone propionate, linezolid, and indomethacin) after intravenous administration in rats. A semi-mechanistic model was used to describe the observed drug concentrations in the trachea, bronchi, and the alveolar parenchyma based on tissue specific affinities (Kp) and blood flows. The model-based analysis was able to explain the pulmonary pharmacokinetics (PK) of the two neutral and one basic model drugs, suggesting up to six-fold differences in Kp between trachea and alveolar parenchyma for salmeterol. Applying the same principles, it was not possible to predict the pulmonary PK of indomethacin, indicating that acidic drugs might show different pulmonary PK characteristics. The separate estimates for local Kp, tracheal and bronchial blood flow were reported for the first time. This work highlights the importance of lung physiology- and drug-specific parameters for regional pulmonary tissue retention. Its understanding is key to optimize inhaled drugs for lung diseases. [ABSTRACT FROM AUTHOR]

Itraconazole distribution is largely dependent on its high liposolubility. Intrapulmonary lung concentrations remain unknown in haematological patients. We report itraconazole lung concentrations in such patients treated with itraconazole. Itraconazole and hydroxy-itraconazole were measured by high-performance liquid chromatography in concomitant blood samples and lung post-mortem biopsies (three cases) or lung lobectomy (one case). These itraconazole and metabolite lung concentrations were sufficient to be active on Aspergillus. [ABSTRACT FROM AUTHOR]