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 biologies,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.
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 biologies,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.
基金
supported by National Natural Science Foundation of China(grants:81573489,81522047,81730103,81320108027,81660618,and 81773808)
the National Key Research and Development Program(grant:2017YFE0109900 and 2017YFC0909303,China)
the 111 project(grant:B16047,China)
the Key Laboratory Foundation of Guangdong Province(grant:2017B030314030,China)
Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)
National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China)
Natural Science Foundation of Guangdong(grant:2017A030311018 and 2015A030313124,China)
National Institutes of Health(grants No.R01CA225958 and R01GM113888 to Ai-Ming Yu,USA).
