Data Science and Digital Solutions, Alcon Vision LLC, Fort Worth, TX, USA.
Data Science and Digital Solutions, Alcon Vision LLC, Fort Worth, TX, USA.
Drug Discov Today. 2019 Aug;24(8):1551-1563. doi: 10.1016/j.drudis.2019.05.039. Epub 2019 Jul 15.
By explicitly representing ocular anatomy, computational fluid dynamic simulation methods model drug mass transport both within and between ocular tissue regions, providing reliable animal-to-human translation of bioavailability. Here, we apply physiologically based models to simulate ocular drug administration. A non-anatomical model is used that applies a simple theorem for calculating ocular bioavailability from a topical dose. A computational fluid dynamic model is also described that incorporates ocular physiology in anatomical models for rabbit, monkey and man. This second method applies material properties and boundary conditions for various tissues enabling simulation of fluid flows, pressures, temperatures, convection, and drug advection following various modes of administration. The method provides a regional distribution with a given tissue not available using standard compartmental models, and enables translation of results from animal experiments into predictions for human ocular pharmacokinetics (PK).
通过明确表示眼部解剖结构，计算流体动力学模拟方法可以模拟药物在眼部组织区域内和之间的质量传递，从而可靠地将生物利用度从动物转化到人类。在这里，我们应用基于生理学的模型来模拟眼部药物给药。使用一种非解剖模型，该模型应用一个简单的定理来计算局部剂量的眼部生物利用度。还描述了一种计算流体动力学模型，该模型将眼部生理学纳入兔、猴和人的解剖模型中。第二种方法适用于各种组织的材料特性和边界条件，从而能够模拟给药后各种模式下的流体流动、压力、温度、对流和药物对流。该方法提供了一种给定组织的区域分布，这是使用标准隔室模型无法获得的，并且能够将动物实验的结果转化为对人类眼部药代动力学（PK）的预测。
