Development of quantitative evaluation method of the drug transport systems at the blood brain barrier which influences the CNS effect.

本研究以血脑屏障中表达的药物转运体为研究对象，旨在建立此类药物转运体影响的定量评价方法。基因敲除小鼠的体内研究表明，在血脑屏障处被ABC转运蛋白、Mrp4、P-gp和Bcrp积极挤出的药物，对中枢神经系统的渗透有限。本研究还阐明了由Oat3从中枢神经系统中去除的药物。与Mrp4一起，Oat3形成有效的定向运输，穿过血脑屏障。本研究还发现了一些适用于PET研究的转运体底物。

This study focused on the drug transporters expressed in the blood-brain barrier, and aimed at developing quantitative evaluation method of the impact of such drug transporters. In vivo studies using knockout mice elucidated that drugs that are actively extruded by ABC transporters, Mrp4, P-gp and Bcrp at the blood-brain barrier, and thereby, showing limited penetration into the central nervous system. This study also elucidated drugs that are removed by Oat3 from the central nervous system. In conjunction with Mrp4, Oat3 forms efficient directional transport across the blood-brain barrier. This study also found some transporter substrates applicable to PET study.