Current trends in drug metabolism and pharmacokinetics

被引:170
|
作者
Li, Yuhua [1 ,2 ]
Meng, Qiang [3 ]
Yang, Mengbi [4 ]
Liu, Dongyang [5 ]
Hou, Xiangyu [6 ]
Tang, Lan [7 ]
Wang, Xin [8 ]
Lyu, Yuanfeng [4 ]
Chen, Xiaoyan [6 ]
Liu, Kexin [3 ]
Yu, Ai-Ming [9 ]
Zuo, Zhong [4 ]
Bi, Huichang [1 ]
机构
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510275, Guangdong, Peoples R China
[2] Nanchang Univ, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China
[3] Dalian Med Univ, Coll Pharm, Dalian 116044, Peoples R China
[4] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Peoples R China
[5] Peking Univ, Hosp 3, Drug Clin Trial Ctr, Beijing 100191, Peoples R China
[6] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
[7] Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Guangdong, Peoples R China
[8] East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China
[9] Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
Pharmacokinetics; Drug metabolism; Drug-drug interactions; Modeling; Metabolizing enzymes; Transporters; Nuclear receptors; Noncoding RNAs; ARYL-HYDROCARBON RECEPTOR; BLOOD-BRAIN-BARRIER; ORGANIC ANION TRANSPORTERS; CHRONIC KIDNEY-DISEASE; PREGNANE-X-RECEPTOR; P-GLYCOPROTEIN; QUANTITATIVE PREDICTION; CYTOCHROME-P450; ENZYMES; DOWN-REGULATION; IN-VIVO;
D O I
10.1016/j.apsb.2019.10.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 drugs and 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 modeling 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. (C) 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
引用
收藏
页码:1113 / 1144
页数:32
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