The effect of chronic renal failure on drug metabolism and transport.
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.
Dreisbach
Albert W
AW
University of Mississippi Medical Center, Division of Nephrology, Department of Medicine, 2500 North State Street, Jackson, MS 39216, USA. adreisbach@umsmed.edu
Lertora
Juan J L
JJ
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
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System