| 疾病状态下的药物代谢处置变化及其机制研究 |
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| 引用本文： | 张晓芳,周芳,王广基,张经纬.疾病状态下的药物代谢处置变化及其机制研究[J].现代药物与临床,2019,42(3):369-377. |
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| 作者姓名： | 张晓芳 周芳 王广基 张经纬 |
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| 作者单位： | 中国药科大学药物代谢动力学重点实验室, 江苏 南京 210009,中国药科大学药物代谢动力学重点实验室, 江苏 南京 210009,中国药科大学药物代谢动力学重点实验室, 江苏 南京 210009,中国药科大学药物代谢动力学重点实验室, 江苏 南京 210009 |
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| 基金项目： | 国家自然科学基金（81573494，81803625，81573496）；江苏省自然科学基金（BK20160076，BK20180558） |
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| 摘 要： | 疾病状态下药物代谢酶和药物转运体的异常调控会引起药物动力学过程的改变，进而影响药物疗效，甚至增加不良反应发生的风险。代谢酶/转运体异常调控的机制主要涉及炎症相关的信号通路/核受体、表观遗传修饰和蛋白质翻译后修饰等。系统回顾并总结了几类主要常见疾病状态下的药物代谢酶/转运体的调控变化及相关机制，同时介绍了生理药动学模型在指导疾病患者临床合理用药方面的应用，以期为基于疾病状态下药物代谢酶/转运体的安全有效的个体化用药提供借鉴和思路。
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| 关 键 词： | 疾病 代谢酶/转运体 调控机制 生理药动学模型 合理用药 |
| 收稿时间： | 2018/12/24 0:00:00 |
Changes and related mechanisms of drug metabolism and disposition under diseases status |
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| ZHANG Xiaofang,ZHOU Fang,WANG Guangji and ZHANG Jingwei.Changes and related mechanisms of drug metabolism and disposition under diseases status[J].Drugs & Clinic,2019,42(3):369-377. |
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| Authors: | ZHANG Xiaofang ZHOU Fang WANG Guangji and ZHANG Jingwei |
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| Institution: | Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China,Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China,Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China and Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China |
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| Abstract: | Dysregulation of drug metabolizing enzymes and transporters (DMET) during diseases leads to altered pharmacokinetics.It has profound impact on drug safety and efficacy.The mechanisms of this dysregulation include inflammation associated signal pathway/nuclear receptor,epigenetic regulation and post-translational modification.This article reviews the regulation of DMET under disease status and its related mechanisms.The application of physiologically-based pharmacokinetic model in rational drug usage in patients is also summarized.Our work will benefit personalized medicine according to DMET phenotype. |
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| Keywords: | disease drug metabolizing enzyme and transporter regulating mechanism physiologically-based pharmacokinetic model rational usage of medicines |
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