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The influence of chronic renal failure on drug metabolism and transport

A W Dreisbach1

  • 1Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. adreisbach@umsmed.edu

Clinical Pharmacology and Therapeutics
|September 25, 2009
PubMed

Insights

Chronic renal failure (CRF) impairs drug metabolism and transport. This affects how the body processes medications, increasing the risk of adverse drug reactions in patients with kidney disease.

Area of Science:

  • Pharmacology
  • Nephrology
  • Drug Metabolism

Background:

  • Chronic renal failure (CRF) impacts drug disposition.
  • Nonrenal clearance and drug bioavailability are significantly reduced in CRF.
  • Phase II metabolic reactions and key drug transporters (P-gp, OATP) are affected.

Purpose of the Study:

  • To elucidate the effects of CRF on drug metabolism and transport.
  • To identify the mechanisms underlying altered drug disposition in CRF.
  • To highlight the clinical significance of these changes for drug safety.

Main Methods:

  • Review of animal models and clinical studies on CRF and drug disposition.
  • Analysis of the impact of CRF on Phase II reactions and drug transporters (P-gp, OATP).
  • Investigation of the role of uremic toxins, PTH, and cytokines.

Main Results:

  • CRF significantly reduces nonrenal clearance and alters drug bioavailability.
  • Drug transporters like P-gp and OATP, and Phase II reactions are impaired.
  • Elevated PTH, cytokines, and uremic toxins contribute to these alterations.

Conclusions:

  • CRF profoundly affects drug disposition, altering metabolism and transport.
  • These changes increase the risk of adverse drug reactions in patients with kidney disease.
  • Understanding these effects is crucial for optimizing pharmacotherapy in CRF.

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