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.
Non-alcoholic fatty liver disease(NAFLD)has become the leading cause of chronic liver disease in adults and children worldwide.The symptoms of NAFLD range from simple steatosis and non-alcoholic stea-tohepatitis(NASH)to hepatic fibrosis or cirrhosis,even ultimately develops to hepatocellular carcinoma.Nuclear receptors(NRs)are a superfamily of ligand-activated transcription factors,most of which are ligand-activated that control cellular homeostasis in the liver and other tissues.A growing number of studies demonstrated the important role of NRs in NAFLD.In this review,the current findings on the role of NRs in NAFLD are summarized and future perspectives to target NRs for NAFLD are discussed.
