Chapter 7:The Characteristics, Validation and Applications of In silico and In vitro Models of Drug Transporters
Chapter 7:The Characteristics, Validation and Applications of In silico and In vitro Models of Drug Transporters
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第 7 章：药物转运蛋白的计算机和体外模型的特征、验证和应用
DOI：
10.1039/9781782623793-00229
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
K. Fenner
中科院分区：
文献类型：
--
作者：
Pradeep Sharma;M. Atari;R. Elsby;Simon Thomas;S. Stahl;C. Hilgendorf;K. Fenner
开发用于药物转运蛋白研究的计算机模拟和体外模型对于了解药代动力学、评估药物间相互作用（DDI）和毒性以及识别由于转运蛋白的参与而导致的药物反应的变异性非常重要。文献中报告了大量不同类型的计算机模拟和体外模型用于转运蛋白研究。这些模型被用作新化学实体的初级筛选，并且在早期开发阶段具有高通量能力的潜力。药物转运蛋白的体外模型应能够精确和准确地确定底物或抑制剂的动力学参数（例如Km、Vmax和IC 50），同时是能够常规使用的稳健系统。本章的目的是系统地介绍各种在硅片和在体外转运蛋白模型，全面分析主要模型可用于转运蛋白的研究，并严格概述每个的优点，缺点和应用。验证的体外试验/模型和体外参数从这些模型中产生的药物药代动力学，DDI和安全性的预测，其效用也进行了讨论。
Development of in silico and in vitro models for drug transporter studies is important to understand the pharmacokinetics, assess drug–drug interactions (DDIs) and toxicities, and to recognise variability in drug response due to the involvement of transporters. A large number of different types of in silico and in vitro models are reported in the literature for transporter studies. These models are used as primary screens for new chemical entities and have the potential of high throughput capacity at the early development stage. In vitro models for a drug transporter should be able to determine kinetic parameters (for e.g. Km, Vmax and IC50) of substrates or inhibitors precisely and accurately whilst being a robust system able to be used on a routine basis. This chapter aims to systematically introduce various in silico and in vitro transporter models, comprehensively analyse major models available for transporter studies, and critically outline the advantages, disadvantages and applications of each. Validation of in vitro assays/models and in vitro parameters generated from these models is also discussed in light of their utility in the prediction of drug pharmacokinetics, DDIs and safety.