Chapter 6: Drug Transporters in the Lung: Expression and Potential Impact on Pulmonary Drug Disposition
Published:16 Aug 2016
L. Gustavsson, C. Bosquillon, M. Gumbleton, T. Hegelund-Myrbäck, T. Nakanishi, D. Price, ... X. Zhou, in Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development, ed. G. Nicholls, K. Youdim, G. Nicholls, and K. Youdim, The Royal Society of Chemistry, 2016, vol. 1, ch. 6, pp. 184-228.
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Several drug transporters of the solute carrier (SLC and SLCO) and ATP binding cassette (ABC) families are expressed in the lung, and it is now known that active transport processes may affect the local pulmonary disposition of drugs administered directly to the lung, as well as being involved in the uptake of drugs to the lung from the systemic circulation. Organic cation transporters, peptide transporters and P-glycoprotein are examples of transport proteins that have been demonstrated to influence pulmonary drug disposition. The evidence for the functional importance of drug transporters in the lung is based mainly on in vitro cell and isolated perfused lung models, and it has proved to be a major challenge to translate these data to the in vivo situation. This is, in part, due to the complex anatomical structure of the lung, which contains a variety of cell types with different morphological and functional features as well as different spatial distributions. The potential impact of membrane transporters in the lung is an important emerging research area that in the future may enable rational design of drugs for the treatment of respiratory diseases and increase our potential to understand mechanisms of pulmonary toxicity. In this chapter, the current literature on drug transporter expression in the lung, the transporters’ functional impact as well as models used to study pulmonary drug disposition are reviewed.