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Current Trends in Drug Metabolism and Pharmacokinetics
Acta Pharmaceutica Sinica B ( IF 14.5 ) Pub Date : 2019-10-18 , DOI: 10.1016/j.apsb.2019.10.001
Yuhua Li , Qiang Meng , Mengbi Yang , Dongyang Liu , Xiangyu Hou , Lan Tang , Xin Wang , Yuanfeng Lyu , Xiaoyan Chen , Kexin Liu , Ai-Ming Yu , Zhong Zuo , Huichang Bi

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug–drug interactions, especially interactions between drugs and herbs, between therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.



中文翻译:

药物代谢和药代动力学的最新趋势

药代动力学(PK)是对药物的吸收,分布,代谢和排泄(ADME)过程的研究。了解PK特性对于药物开发和精准药物治疗至关重要。在这篇综述中,我们概述了有关PK的最新研究,重点是以下几个方面:(1)在确定PK方面药物代谢酶和转运蛋白的更新,以及外源生物受体和非编码RNA(ncRNA)的进展在PK的调节中,提供了对导致药物治疗个体间差异的转录和转录后调控机制的新认识;(2)评估药物相互作用的现状和趋势,尤其是药物与草药之间,治疗性生物制剂之间以及微生物群介导的相互作用之间的相互作用;(3)在了解疾病对PK的影响方面的进展,特别是随着疾病进展的代谢酶和转运蛋白的变化;(4)数学建模的趋势,包括基于生理的PK和新颖的动物模型,例如用于DMPK研究的基于CRISPR / Cas9的动物模型;(5)新兴的非经典异种生物代谢途径和新型代谢酶(特别是非P450s)的参与。讨论了现有的挑战和对未来方向的看法,并可能刺激新的研究模型,技术和策略的发展,以开发更好的药物和改善临床实践。(4)数学建模的趋势,包括基于生理的PK和新颖的动物模型,例如用于DMPK研究的基于CRISPR / Cas9的动物模型;(5)新兴的非经典异种生物代谢途径和新型代谢酶(特别是非P450s)的参与。讨论了现有的挑战和对未来方向的看法,并可能刺激新的研究模型,技术和策略的发展,以开发更好的药物和改善临床实践。(4)数学建模的趋势,包括基于生理的PK和新颖的动物模型,例如用于DMPK研究的基于CRISPR / Cas9的动物模型;(5)新兴的非经典异种生物代谢途径和新型代谢酶(特别是非P450s)的参与。讨论了现有的挑战和对未来方向的看法,并可能刺激新的研究模型,技术和策略的发展,以开发更好的药物和改善临床实践。

更新日期:2019-10-19
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