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Review
. 2008 Aug;4(8):1065-74.
doi: 10.1517/17425255.4.8.1065.

The effect of chronic renal failure on drug metabolism and transport

Albert W Dreisbach  1 , Juan J L Lertora
Affiliations
Review

The effect of chronic renal failure on drug metabolism and transport

Albert W Dreisbach et al. Expert Opin Drug Metab Toxicol. 2008 Aug.

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.

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Conflict of interest statement

Declaration of Interest: The authors state no conflict of interests and have received no payment in the preparation of this manuscript.

Figures

Figure 1
Figure 1
Summary of Physiological and Pharmacologic Effects of CRF on Drug Metabolism and Transport.
See this image and copyright information in PMC

References

    1. Reidenberg MM. Chapter 3, Drug metabolism in uremia, in Renal function and drug action. Philadelphia: Saunders; 1971. pp. 19–32.

    2. First Book to address the effect of renal failure on drug metabolism pathways

    1. Gibson TP. Renal disease and drug metabolism: an overview. Am J Kidney Dis. 1986;8(1):7–17. - PubMed
    1. Touchette MA, Slaughter RL. The effect of renal failure on hepatic drug clearance. DICP Ann Pharmacother. 1991;25:1214–24. - PubMed
    1. Elston AC, Bayliss MK, Park GR. Effect of renal failure on drug metabolism by the liver. Brit J Anaesth. 1993;71:282–290. - PubMed
    1. Talbert RL. Drug dosing in renal insufficiency. J Clin Pharmacol. 1994;34:99–110. - PubMed

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