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

The effect of chronic renal failure on drug metabolism and transport.

Author information

1
University of Mississippi Medical Center, Division of Nephrology, Department of Medicine, 2500 North State Street, Jackson, MS 39216, USA. adreisbach@umsmed.edu

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.

PMID:
18680441
PMCID:
PMC2745294
DOI:
10.1517/17425255.4.8.1065
[Indexed for MEDLINE]
Free PMC Article

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