期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 99, 期 5, 页码 2240-2255出版社
WILEY
DOI: 10.1002/jps.21995
关键词
drug inhalation; pulmonary delivery; multidrug resistance transporters; peptide transporters; organic cation transporters; organic anion transporters; Calu-3 cells; isolated perfused lungs; cell culture; permeability
The role of transporters in drug absorption, distribution and elimination processes as well as in drug drug interactions is increasingly being recognised. Although the lungs express high levels of both efflux and uptake drug transporters, little is known of the implications for the biopharmaceutics of inhaled drugs. The current knowledge of the expression, localisation and functionality of drug transporters in the pulmonary tissue and the few studies that have looked at their impact on pulmonary drug absorption is extensively reviewed. The emphasis is on transporters most likely to affect the disposition of inhaled drugs: (1) the ATP-binding cassette (ABC) superfamily which includes the efflux pumps P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs), breast cancer resistance protein (BCRP) and (2) the solute-linked carrier (SLC and SLCO) superfamily to which belong the organic cation transporter (OCT) family, the peptide transporter (PEPT) family, the organic anion transporter (OAT) family and the organic anion transporting polypeptide (OATP) family. Whenever available, expression and localisation in the intact human tissue are compared with those in animal lungs and respiratory epithelial cell models in vitro. The influence of lung diseases or exogenous agents on transporter expression is also mentioned. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2240-2255, 2010
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