Funk Christoph
F Hoffmann-La Roche Ltd, Non-Clinical Development - Drug Safety, 4070 Basel, Switzerland.
Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):363-79. doi: 10.1517/17425255.4.4.363.
Hepatic drug transporters of the solute carrier (OATPs, OAT2, OCT1, NTCP) and ABC transporter superfamilies (MDR1, MRPs, BCRP, BSEP) can significantly modulate drug ADME routes.
The currently available literature was reviewed with focus on hepatic drug transporters, related drug-drug interactions and available tools for transporter assessment and extrapolation to in vivo.
Hepatic drug transporters have gained additional importance in drug clearance by optimization for basic DMPK properties early on in drug research. However, the lack of selective substrates and inhibitors, proper assessment of the kinetic properties due to interfering passive permeability and multiple binding sites, as well as endogenous transporters present in many cellular assays, are some of the hurdles in studying active drug transport processes. Therefore, data from these in vitro assays have to be carefully evaluated to allow sound extrapolation to the in vivo situation.
溶质载体家族（有机阴离子转运多肽、OAT2、有机阳离子转运体1、钠-牛磺胆酸共转运多肽）和ABC转运体超家族（多药耐药蛋白1、多药耐药相关蛋白、乳腺癌耐药蛋白、胆盐输出泵）的肝脏药物转运体可显著调节药物的吸收、分布、代谢和排泄途径。
综述当前可得文献，重点关注肝脏药物转运体、相关药物-药物相互作用以及用于转运体评估和体内外推的可用工具。
通过在药物研究早期优化基本的药物代谢动力学性质，肝脏药物转运体在药物清除中变得更加重要。然而，缺乏选择性底物和抑制剂、由于干扰性被动通透性和多个结合位点导致的动力学性质评估不当，以及许多细胞试验中存在的内源性转运体，是研究药物主动转运过程的一些障碍。因此，必须仔细评估这些体外试验的数据，以便合理地外推至体内情况。
