Gatarić Biljana, Parojčić Jelena
Department of Pharmaceutical Technology and Cosmetology, University of Banja Luka - Faculty of Medicine, Save Mrkalja 14, 78000, Banja Luka, Bosnia and Hercegovina.
Department of Pharmaceutical Technology and Cosmetology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia.
Biopharm Drug Dispos. 2019 Feb;40(2):51-61. doi: 10.1002/bdd.2170. Epub 2019 Feb 11.
Solubility and permeability are recognized as key parameters governing drug intestinal absorption and represent the basis for biopharmaceutics drug classification. The Biopharmaceutics Classification System (BCS) is widely accepted and adopted by regulatory agencies. However, currently established low/high permeability and solubility boundaries are the subject of the ongoing scientific discussion. The aim of the present study was to apply data mining analysis on the selected drugs data set in order to develop a human permeability predictive model based on selected molecular descriptors, and to perform data clustering and classification to identify drug subclasses with respect to dose/solubility ratio (D/S) and effective permeability (P ). The P values predicted for 30 model drugs for which experimental human permeability data are not available were in good agreement with the reported fraction of drug absorbed. The results of clustering and classification analysis indicate the predominant influence of P over D/S. Two P cut-off values (1 × 10 and 2.7 × 10 cm/s) have been identified indicating the existence of an intermediate group of drugs with moderate permeability. Advanced computational analysis employed in the present study enabled the recognition of complex relationships and patterns within physicochemical and biopharmaceutical properties associated with drug bioperformance.
溶解度和渗透性被认为是决定药物肠道吸收的关键参数，也是生物药剂学药物分类的基础。生物药剂学分类系统（BCS）已被监管机构广泛接受和采用。然而，目前确定的低/高渗透性和溶解度界限仍是正在进行的科学讨论的主题。本研究的目的是对选定的药物数据集进行数据挖掘分析，以便基于选定的分子描述符开发一种人体渗透性预测模型，并进行数据聚类和分类，以识别关于剂量/溶解度比（D/S）和有效渗透率（P）的药物亚类。对30种无实验人体渗透性数据的模型药物预测的P值与报道的药物吸收分数高度一致。聚类和分类分析结果表明P对D/S的影响占主导地位。已确定两个P临界值（1×10和2.7×10 cm/s），表明存在一组具有中等渗透性的中间药物。本研究采用的先进计算分析能够识别与药物生物性能相关的物理化学和生物药剂学性质中的复杂关系和模式。
