Metabolic Enzyme System and Transport Pathways in Chronic Kidney Diseases

Current Drug Metabolism
Bin LiuJie Peng

Abstract

Chronic Kidney Disease (CKD), a global public health problem, affects numerous people worldwide, and the prevalence is rising. Results from animal experiments and clinical investigations have demonstrated that drug metabolic enzymes and transporters-mediated non-renal clearance are dramatically impaired in CKD, co-respondent with alterations in the elimination of metabolized drugs. Accumulated uremic toxins may downregulate or directly inhibit the activity and/or the expression of drug metabolic enzymes and transporters, which may result in unintended alterations of drug exposure and response in cases when drugs dose are not adjusted for the renal dysfunction. The aim of this review is to highlight the impact of CKD on non-renal drug clearance involving metabolism enzyme system and transport pathways, and to provide insight into the impact of non-renal drug clearance on drug metabolism and distribution in CKD patients. Metabolic enzyme system and transport pathways are dysregulated in both rats and humans with renal failure. The alterations of drug metabolic enzymes and transporters in the kidney, liver, and intestine play an important role in their pharmacokinetic changes, and thus, the metabolism and transportation of many me...Continue Reading

Citations

Jul 19, 2019·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Abolfazl RazzaghdoustMasoumeh Zangeneh
Jul 22, 2018·Toxins·Björn MeijersPieter Evenepoel
Feb 8, 2019·Nature Reviews. Nephrology·Sanjay K Nigam, Kevin T Bush
Oct 13, 2020·Nucleic Acids Research·Jiayi YinFeng Zhu
Nov 10, 2020·European Journal of Drug Metabolism and Pharmacokinetics·Dorien Groenendaal-van de MeentMartin den Adel

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