根据结构参数和理化特性预测药物口服后的首过代谢过程

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Mir Amir Hossein Hosseini, Ali Akbar Alizadeh, Ali Shayanfar
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引用次数: 0

摘要

背景和目的:口服首过代谢是影响药物药代动力学特征的关键因素。根据化学结构参数预测口服首过代谢对药物设计过程非常有用。开发具有可接受的药代动力学特征的口服药物,对于减少在临床前研究中评估候选化合物的首过代谢程度所需的成本和时间非常必要。本研究旨在估算口服药物的首过代谢:方法:研究人员收集了一组有首过代谢数据报告的化合物。此外,还从文献中提取了人体肠道吸收率和口服生物利用度数据,从而提出了一个分类系统,根据药物的首过代谢程度将其分开。计算了每种化合物的各种结构参数。利用逻辑回归法得出了每种化合物的结构和理化值与化合物所属类别的关系:初步分析表明,logD7.4 > 1 或崎岖系数 > 1.5 的化合物更有可能具有较高的首过代谢率。结果:初步分析表明,logD7.4 > 1 或凹凸因子 > 1.5 的化合物更有可能具有较高的首过代谢率。这些模型的总体准确率在 72%(使用简单描述因子的模型)到 78%(使用复杂描述因子的模型)之间。虽然与复杂模型相比,使用简单描述符的模型的准确率较低,但它们的可解释性更强,更易于研究人员使用:结论:根据口服首过代谢的程度对药物进行了新的分类,并建立了机理模型,以便将候选化合物归入适当的拟议类别。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Prediction of the First-Pass Metabolism of a Drug After Oral Intake Based on Structural Parameters and Physicochemical Properties.

Prediction of the First-Pass Metabolism of a Drug After Oral Intake Based on Structural Parameters and Physicochemical Properties.

Background and objective: The oral first-pass metabolism is a crucial factor that plays a key role in a drug's pharmacokinetic profile. Prediction of the oral first-pass metabolism based on chemical structural parameters can be useful in the drug-design process. Developing an orally administered drug with an acceptable pharmacokinetic profile is necessary to reduce the cost and time associated with evaluating the extent of the first-pass metabolism of a candidate compound in preclinical studies. The aim of this study is to estimate the first-pass metabolism of an orally administered drug.

Methods: A set of compounds with reported first-pass metabolism data were collected. Moreover, human intestinal absorption percentage and oral bioavailability data were extracted from the literature to propose a classification system that split the drugs up based on their first-pass metabolism extents. Various structural parameters were calculated for each compound. The relations of the structural and physicochemical values of each compound to the class the compound belongs to were obtained using logistic regression.

Results: Initial analysis showed that compounds with logD7.4 > 1 or a rugosity factor of > 1.5 are more likely to have high first-pass metabolism. Four different models that can predict the oral first-pass metabolism with acceptable error were introduced. The overall accuracies of the models were in the range of 72% (for models with simple descriptors) to 78% (for models with complex descriptors). Although the models with simple descriptors have lower accuracies compared to complex models, they are more interpretable and easier for researchers to utilize.

Conclusion: A novel classification of drugs based on the extent of the oral first-pass metabolism was introduced, and mechanistic models were developed to assign candidate compounds to the appropriate proposed classes.

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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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