Prediction of Biopharmaceutical Drug Disposition Classification System (BDDCS) by Structural Parameters
Prediction of Biopharmaceutical Drug Disposition Classification System (BDDCS) by Structural Parameters
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DOI：
10.18433/jpps30271
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发表时间：
2019-06-21
影响因子：
2.7
通讯作者：
Shayanfar, Ali
中科院分区：
文献类型：
--
作者：
Golfar, Yeganeh;Shayanfar, Ali
药物的理化和药动学性质的建模对于药物发现和开发中的预测和机理表征是重要的。生物药剂学药物处置分类系统（BDDCS）是基于溶解度和代谢的四类系统。该系统用于描述转运蛋白在药代动力学中的作用及其与代谢酶的相互作用。它进一步预测药物在肝脏和肠道中的分布和潜在的药物相互作用。根据BDDCS，药物根据代谢程度和溶解度（高和低）分为四组。本研究以药物的结构参数为基础，通过ACD/Labs软件计算药物的结构描述符（Abraham溶剂化参数和正辛醇-水分配系数），收集文献报道的药物的BDDCS数据，建立基于分类的BDDCS分类预测模型。将数据分为训练集和测试集。结果表明，log P和Abraham溶剂化参数能够较好地预测药物在BDDCS体系中的溶解度和代谢情况，并具有较好的预测精度。基于所建立的溶解度和代谢类别预测方法，BDDCS的溶解度和代谢类别预测准确度较高，而药物的结构特征，即logP和Abraham溶剂化参数（极化率、氢键酸碱度）能够准确预测BDDCS的溶解度和代谢类别。
Modeling of physicochemical and pharmacokinetic properties is important for the prediction and mechanism characterization in drug discovery and development. Biopharmaceutics Drug Disposition Classification System (BDDCS) is a four-class system based on solubility and metabolism. This system is employed to delineate the role of transporters in pharmacokinetics and their interaction with metabolizing enzymes. It further anticipates drug disposition and potential drug-drug interactions in the liver and intestine. According to BDDCS, drugs are classified into four groups in terms of the extent of metabolism and solubility (high and low). In this study, structural parameters of drugs were used to develop classification-based models for the prediction of BDDCS class.Reported BDDCS data of drugs were collected from the literature, and structural descriptors (Abraham solvation parameters and octanol-water partition coefficient (log P)) were calculated by ACD/Labs software. Data were divided into training and test sets. Classification-based models were then used to predict the class of each drug in BDDCS system using structural parameters and the validity of the established models was evaluated by an external test set.The results of this study showed that log P and Abraham solvation parameters are able to predict the class of solubility and metabolism in BDDCS system with good accuracy. Based on the developed methods for prediction solubility and metabolism class, BDDCS could be predicted in the correct with an acceptable accuracy.Structural properties of drugs, i.e. logP and Abraham solvation parameters (polarizability, hydrogen bonding acidity and basicity), are capable of estimating the class of solubility and metabolism with an acceptable accuracy.