Application of In Silico, In Vitro and Preclinical Pharmacokinetic Data for the Effective and Efficient Prediction of Human Pharmacokinetics
Application of In Silico, In Vitro and Preclinical Pharmacokinetic Data for the Effective and Efficient Prediction of Human Pharmacokinetics
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DOI：
10.1021/mp300476z
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发表时间：
2013-04-01
影响因子：
4.9
通讯作者：
McGinnity, Dermot F.
中科院分区：
文献类型：
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作者：
Grime, Kenneth H.;Barton, Patrick;McGinnity, Dermot F.
在当今的制药研发时代，决策数据的集中交付比以往任何时候都更加迫切。由于几年的成功，失败和相应的学习，本文还提供了建议和指导，在体外和体内实验进行，以促进有效和成本效益的追求候选药物与可接受的人体药代动力学曲线。预测的计算机模型是重要的指导设计的化合物具有最高的概率有合适的DMPK属性，而不是在预测人体药代动力学本身，和这种方法的价值和实用性进行审查，旨在提供方向DMPK科学家。针对吸收、分布、消除和有效半衰期，介绍了各种战略，以便为常见情况提供指导。
In the present age of pharmaceutical research and development, focused delivery of decision making data is more imperative than ever before. Resulting from several years' success, failure and consequential learning, this article also proffers advice and guidance on which in vitro and in vivo experiments to perform to facilitate efficient and cost-effective pursuit of candidate drugs with acceptable human pharmacokinetic profiles. Predictive in silico models are important in directing design toward compounds with the highest probability of having suitable DMPK properties rather than in predicting human pharmacokinetics per se, and the value and utility of such approaches are reviewed with the intention of providing direction to DMPK scientists. Relating to absorption, distribution, elimination and effective half-life, strategies are described to provide direction in commonly encountered scenarios.