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口服药物吸收的预测模型:从计算机模拟方法到综合动力学模型。

Predictive models for oral drug absorption: from in silico methods to integrated dynamical models.

作者信息

Dokoumetzidis Aristides, Kalantzi Lida, Fotaki Nikoletta

机构信息

University of Manchester, School of Pharmacy and Pharmaceutical Sciences, Stopford Building , Manchester, M13 9PT , UK.

出版信息

Expert Opin Drug Metab Toxicol. 2007 Aug;3(4):491-505. doi: 10.1517/17425225.3.4.491.

Abstract

Poor oral absorption is one of the most common reasons for a drug to be terminated during development. Oral drug absorption is a complex process affected by many competing factors related to the compound, the formulation and the gastrointestinal physiology. Throughout drug development, in silico, computational and mathematical models play important roles in the support of drug development and decision making in absorption-related issues. These models range from simple empirical rule of thumb tools to sophisticated dynamic systems. This article reviews the different computational methods for oral drug absorption for the various processes, with emphasis on solubility, permeability, dissolution and release rates, and gastrointestinal transit, but also on the modern integrated absorption prediction systems and computer software.

摘要

口服吸收不佳是药物在研发过程中被终止的最常见原因之一。口服药物吸收是一个复杂的过程,受到许多与化合物、制剂和胃肠生理学相关的相互竞争因素的影响。在整个药物研发过程中,计算机模拟、计算和数学模型在支持药物研发以及解决吸收相关问题的决策中发挥着重要作用。这些模型从简单的经验法则工具到复杂的动态系统不等。本文综述了针对口服药物吸收各个过程的不同计算方法,重点关注溶解度、渗透性、溶解和释放速率以及胃肠转运,同时也涉及现代综合吸收预测系统和计算机软件。

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