Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG72RD, United Kingdom.
J Pharm Sci. 2010 May;99(5):2240-55. doi: 10.1002/jps.21995.
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.
转运体在药物吸收、分布和消除过程以及药物-药物相互作用中的作用正日益受到重视。尽管肺部表达高水平的外排和摄取药物转运体，但对于吸入药物的生物药剂学的影响知之甚少。本文广泛综述了肺部组织中药物转运体的表达、定位和功能的现有知识，以及少数研究其对肺部药物吸收影响的研究。重点介绍最有可能影响吸入药物处置的转运体：（1）ATP 结合盒（ABC）超家族，包括外排泵 P-糖蛋白（P-gp）、多药耐药相关蛋白（MRPs）、乳腺癌耐药蛋白（BCRP）和（2）溶质载体（SLC 和 SLCO）超家族，属于有机阳离子转运体（OCT）家族、肽转运体（PEPT）家族、有机阴离子转运体（OAT）家族和有机阴离子转运多肽（OATP）家族。只要有条件，就将完整的人体组织中的表达和定位与动物肺部和体外呼吸道上皮细胞模型中的表达和定位进行比较。还提到了肺部疾病或外源性物质对转运体表达的影响。
