Metcalfe Paul D, Thomas Simon
Cyprotex Discovery Ltd, Macclesfield, SK10 2DR, UK.
Curr Opin Drug Discov Devel. 2010 Jan;13(1):104-10.
To predict the performance of a drug following oral dosing, a thorough understanding of the dissolution, uptake and metabolism of the compound is required. In this review, approaches to in silico modeling of these processes are discussed. Although oral absorption, which is limited by dissolution and passive permeation, is to some extent predictable, bioavailability, which is influenced by first-pass metabolism in the intestines and liver, is much more difficult to predict. Much of the difficulty in predicting oral absorption and bioavailability is in the experimental quantification of solubility in the gastrointestinal tract lumen, membrane permeability, plasma protein binding, metabolism and active transport, rather than the formulating of the mathematical models.
为预测口服给药后药物的性能，需要全面了解该化合物的溶解、吸收和代谢情况。在本综述中，将讨论这些过程的计算机模拟方法。尽管受溶解和被动渗透限制的口服吸收在一定程度上是可预测的，但受肠道和肝脏首过代谢影响的生物利用度则更难预测。预测口服吸收和生物利用度的大部分困难在于对胃肠道管腔内溶解度、膜通透性、血浆蛋白结合、代谢和主动转运进行实验定量，而非数学模型的构建。
