Drug uptake systems in liver and kidney: a historic perspective.

Drug uptake systems in liver and kidney: a historic perspective.
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DOI:
10.1038/clpt.2009.235
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发表时间:
2010-01
影响因子:
6.7
通讯作者:
--
中科院分区:
医学2区
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--
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药物及其代谢产物主要通过排泄进入尿液和胆汁而消除。对整个动物、离体器官、细胞和膜囊泡的研究得出的结论是,不同的运输系统负责运输不同类别的有机化合物(小的、大的、阴离子的、阳离子的)。在20世纪90年代早期,功能表达克隆导致了第一个有机阴离子和阳离子转运蛋白的鉴定。最终,所有参与这些有机化合物摄取的主要转运系统都被克隆和表征,我们知道它们属于SLC22A的OAT和OCT以及SLCO多特异性药物转运蛋白超家族的OATP。今天,我们可以在分子水平上解释为什么小的亲水性有机化合物主要通过尿液排泄,而大的两亲性化合物主要通过胆汁排泄,我们可以开始预测新化合物的药物相互作用。
Drugs and their metabolites are mainly eliminated by excretion into urine and bile. Studies in whole animals, isolated organs, cells and membrane vesicles led to the conclusion that different transport systems are responsible for the transport of different classes of organic compounds (small large, anionic, cationic). In the early 1990's functional expression cloning resulted in the identification of the first transporters for organic anions and cations. Eventually, all the major transport systems involved in the uptake of these organic compounds have been cloned and characterized and we know that they belong to the OATs and OCTs of the SLC22A and the OATPs of the SLCO superfamilies of polyspecific drug transporters. Today we can explain at the molecular level why small and hydrophilic organic compounds are predominantly excreted via urine while large and amphipathic compounds are mainly excreted via bile and we can start to predict drug-drug interactions for new compounds.
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