槲皮素PBPK模型构建及其在人体中药代动力学特征预测
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作者单位:

1.南方医科大学公共卫生学院,广东 广州 510080;2.国家食品安全风险评估中心,北京 100022

作者简介:

徐孥 女 在读研究生 研究方向为公共卫生 E-mail: 1501567529@qq.com

通讯作者:

张磊 男 研究员 研究方向为污染物监测与风险评估 E-mail:zhanglei@cfsa.net.cn
吴永宁 男 研究员 研究方向为食品污染物分析检测及暴露评估 E-mail:wuyongning@cfsa.net.cn

中图分类号:

R155

基金项目:

国家食品安全风险评估中心高层次人才队伍建设项目


Construction of PBPK model of quercetin and predicting pharmacokinetic behavior in humans
Author:
Affiliation:

1.School of Public Health, Southern Medical University, Guangdong Guangzhou 510080, China;2.China National Center for Food Safety Risk Assessment, Beijing 100022, China

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    摘要:

    目的 利用生理药动学(PBPK)模型预测槲皮素在人体内的组织分布特征,并分析其在不同生理房室中的分布与代谢转化过程,从而补充槲皮素人体实验数据的不足,为其健康风险-受益评估及安全摄入量的制定提供技术支撑。方法 基于槲皮素的理化特性、大鼠生理参数及吸收、分布、代谢和排泄参数,利用GastroPlus软件构建大鼠PBPK模型,并对模型所预测的浓度-时间曲线与实测数据进行对比分析,验证所预测的主要药动学参数的准确性。并将该模型进一步外推至人体PBPK模型,进行精度、敏感性和相关性分析。结果 大鼠和人体PBPK模型的主要药动学参数预测值与实测值之比均在0.5~2倍误差范围内,且平均折叠误差和绝对平均折叠误差均处于可接受水平,表明模型拟合良好,预测结果具有较高的可信度。结论 成功构建大鼠生理药动学模型,并且在此基础上外推至人,预测人体药动学行为,为高效安全使用和管理槲皮素提供了理论基础。

    Abstract:

    Objective To use physiologically based pharmacokinetic (PBPK) model to predict the tissue distribution of quercetin in human, and analyze its distribution and metabolic transformation process in different physiological compartments, so as to supplement the deficiency of human experimental data, and provide technical support for health risk-benefit assessment and safe intake formulation of quercetin.Methods Based on the physicochemical properties of quercetin, physiological parameters of rats and ADME parameters, a rat PBPK model was constructed by GastroPlus software. The predicted concentration-time curve of the model was compared with the measured data to verify the accuracy of the main pharmacokinetic parameters. The model is further extrapolated to human PBPK model, and the accuracy, sensitivity and correlation analysis are completed.Results The predicted and measured ratios of major pharmacokinetic parameters of PBPK models in rats and human were within the error range of 0.5 to 2 times, and the average folding error and absolute average folding error were both at acceptable levels, indicating that the model was well fitted and the prediction results were highly reliable.Conclusion The PBPK model of rats was successfully constructed, and based on this model, the human pharmacokinetic behavior was predicted, which provided a theoretical basis for efficient and safe use and management of quercetin.

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徐孥,施妙盈,贾旭东,杨杏芬,张磊,吴永宁.槲皮素PBPK模型构建及其在人体中药代动力学特征预测[J].中国食品卫生杂志,2025,37(2):159-167.

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  • 收稿日期:2025-01-06
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  • 在线发布日期: 2025-06-05
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