The effect of chronic renal failure on drug metabolism and transport
- 4 August 2008
- journal article
- review article
- Published by Informa UK Limited in Expert Opinion on Drug Metabolism & Toxicology
- Vol. 4 (8), 1065-1074
- https://doi.org/10.1517/17425255.4.8.1065
Abstract
Background: Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine. Objectives: The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport. Methods: A search of the National Library of Medicine PubMed was done with terms such as chronic renal failure, cytochrome P450 [CYP], liver metabolism, efflux drug transport and uptake transport, including relevant articles back to 1969. Results: Animal studies in CRF have shown a significant downregulation (40 – 85%) of hepatic and intestinal CYP metabolism. High levels of parathyroid hormone, cytokines and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein and organic anion transporting polypeptide are also affected. Conclusion: CRF alters intestinal, renal and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions.Keywords
This publication has 91 references indexed in Scilit:
- Pharmacokinetics of Calcium Blockers in Patients with Renal Insufficiency and in Geriatric PatientsActa Medica Scandinavica, 2009
- Downregulation of Hepatic Acetylation of Drugs in Chronic Renal FailureJournal of the American Society of Nephrology, 2008
- Role of Orphan Nuclear Receptors in the Regulation of Drug-Metabolising EnzymesClinical Pharmacokinetics, 2003
- Down‐regulation of hepatic cytochrome P450 in chronic renal failure: role of uremic mediatorsBritish Journal of Pharmacology, 2002
- Principles of Drug Administration in Renal InsufficiencyClinical Pharmacokinetics, 1997
- Alteration of Drug-Protein Binding in Renal DiseaseClinical Pharmacokinetics, 1984
- Clinical Pharmacokinetics of MetoclopramideClinical Pharmacokinetics, 1983
- Plasma Protein Binding of d‐Propoxyphene in Normal Subjects and Anephric PatientsThe Journal of Clinical Pharmacology, 1978
- Pharmacokinetics and Effects of Propranolol in Terminal Uraemic Patients and in Patients Undergoing Regular Dialysis Treatment1Clinical Pharmacokinetics, 1976
- Protein Binding of Drugs in Plasma from Patients with Acute Renal FailureActa Pharmacologica et Toxicologica, 1973