Kusuhara Hiroyuki, Sugiyama Yuichi
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
J Control Release. 2002 Jan 17;78(1-3):43-54. doi: 10.1016/s0168-3659(01)00480-1.
Cumulative studies have revealed the importance of transporters in drug disposition in the body. Recently, organic anion transporters such as organic anion transporting polypeptides (OATPs), organic anion transporters (OATs) and multidrug resistance associated proteins (MRPs) have been identified. Their broad substrate specificity as well as the multiplicity of transporter gene products make these transporters suitable detoxification systems in the body. OATPs and OATs are responsible for the hepatic and renal uptake of organic anions, respectively, while MRP2 is a major transporter involved in the biliary excretion of organic anions. OATPs and MRP2 are involved in the hepatobiliary transport of pravastatin and temocaprilat. These are good examples of hepatobiliary transport maximizing their pharmacological effects, but minimizing their side-effects. Taking into consideration tissue-selective expression and substrate specificity, transporters are useful for delivering small molecules to target tissues. MRPs are also suggested to be involved in the barrier function in the small intestine, blood-brain barrier and blood-cerebrospinal fluid barriers by extruding their ligands into the luminal side. In this manuscript, we have summarized recent studies by others and ourselves on the role of these transporters in the tissue selective distribution and elimination of drugs.
累积研究已揭示转运体在药物体内处置中的重要性。最近，已鉴定出有机阴离子转运体，如有机阴离子转运多肽（OATP）、有机阴离子转运体（OAT）和多药耐药相关蛋白（MRP）。它们广泛的底物特异性以及转运体基因产物的多样性使这些转运体成为体内合适的解毒系统。OATP和OAT分别负责肝脏和肾脏对有机阴离子的摄取，而MRP2是参与有机阴离子胆汁排泄的主要转运体。OATP和MRP2参与普伐他汀和替莫卡普利的肝胆转运。这些是肝胆转运最大化其药理作用但最小化其副作用的良好例子。考虑到组织选择性表达和底物特异性，转运体可用于将小分子递送至靶组织。MRP也被认为通过将其配体挤出到管腔侧而参与小肠、血脑屏障和血脑脊液屏障的屏障功能。在本手稿中，我们总结了他人和我们自己最近关于这些转运体在药物组织选择性分布和消除中的作用的研究。
