Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.

Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.
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DOI:
10.1038/clpt.2013.78
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发表时间:
2013-07
影响因子:
6.7
通讯作者:
--
中科院分区:
医学2区
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药物和代谢物的细胞内浓度通常是疗效、毒性和药物相互作用的重要决定因素。肝脏药物分布可能受许多因素影响,包括理化性质、摄取/外排转运蛋白、蛋白结合、细胞器隔离和代谢。这篇白色论文强调了肝细胞药物/代谢物浓度的决定因素,并提供了用于定量评估肝细胞分子浓度的模型系统、方法和建模/模拟方法的更新。关键的科学差距和未来的研究方向在这一领域进行了讨论。
Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.
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