The effect of chronic renal failure on drug metabolism and transport

Expert Opin Drug Metab Toxicol. 2008 Aug;4(8):1065-74. doi: 10.1517/17425255.4.8.1065.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Biological Transport
  • Clinical Trials as Topic
  • Cytochrome P-450 Enzyme System / metabolism*
  • Down-Regulation
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Kidney Failure, Chronic / metabolism*
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics


  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System