title: The effect of chronic renal failure on drug metabolism and transport.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Mississippi Medical Center, Division of Nephrology, Department of Medicine, 2500 North State Street, Jackson, MS 39216, USA. adreisbach@umsmed.edu
authors.forename: Albert W
authors.initials: AW
authors.lastname: Dreisbach
authors.forename: Juan J L
authors.initials: JJ
authors.lastname: Lertora
mesh_terms: D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015536:Down-Regulation; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System