Abstract
Pharmacokinetic studies conducted in patients with CRF demonstrate that the nonrenal clearance of multiple drugs is reduced. Although the mechanism by which this occurs is unclear, several studies have shown that CRF affects the metabolism of drugs by inhibiting key enzymatic systems in the liver, intestine and kidney. The down-regulation of selected isoforms of the hepatic cytochrome P450 (CYP450) has been reported secondary to a decrease in gene expression. This is associated with major reductions in metabolism of drugs mediated by CYP450. The main hypothesis to explain the decrease in liver CYP450 activity in CRF appears to be the accumulation of circulating factors which can modulate CYP450 activity. Liver phase II metabolic reactions are also reduced in CRF. On the other hand, intestinal drug disposition is affected in CRF. Increased bioavailability of several drugs has been reported in CRF, reflecting decrease in either intestinal first-pass metabolism or extrusion of drugs (mediated by P-glycoprotein). Indeed, intestinal CYP450 is also down-regulated secondary to reduced gene expression, whereas, decreased intestinal P-glycoprotein activity has been described. Finally, although the kidneys play a major role in the excretion of drugs, it has the capacity to metabolize endogenous and exogenous compounds. CRF will lead to a decrease in the ability of the kidney to metabolize drugs, but the repercussions on the systemic clearance of drugs is still poorly defined, except for selected xenobiotics. In conclusion, reduced drug metabolism should be taken into account when evaluating the pharmacokinetics of drugs in patients with CRF.
Keywords: chronic renal failure, cytochrome p450, gene expression, drug metabolism, intestine, liver, serum mediators, p-glycoprotein
Current Drug Metabolism
Title: Drug Metabolism in Chronic Renal Failure
Volume: 4 Issue: 2
Author(s): Vincent Pichette and Francois A. Leblond
Affiliation:
Keywords: chronic renal failure, cytochrome p450, gene expression, drug metabolism, intestine, liver, serum mediators, p-glycoprotein
Abstract: Pharmacokinetic studies conducted in patients with CRF demonstrate that the nonrenal clearance of multiple drugs is reduced. Although the mechanism by which this occurs is unclear, several studies have shown that CRF affects the metabolism of drugs by inhibiting key enzymatic systems in the liver, intestine and kidney. The down-regulation of selected isoforms of the hepatic cytochrome P450 (CYP450) has been reported secondary to a decrease in gene expression. This is associated with major reductions in metabolism of drugs mediated by CYP450. The main hypothesis to explain the decrease in liver CYP450 activity in CRF appears to be the accumulation of circulating factors which can modulate CYP450 activity. Liver phase II metabolic reactions are also reduced in CRF. On the other hand, intestinal drug disposition is affected in CRF. Increased bioavailability of several drugs has been reported in CRF, reflecting decrease in either intestinal first-pass metabolism or extrusion of drugs (mediated by P-glycoprotein). Indeed, intestinal CYP450 is also down-regulated secondary to reduced gene expression, whereas, decreased intestinal P-glycoprotein activity has been described. Finally, although the kidneys play a major role in the excretion of drugs, it has the capacity to metabolize endogenous and exogenous compounds. CRF will lead to a decrease in the ability of the kidney to metabolize drugs, but the repercussions on the systemic clearance of drugs is still poorly defined, except for selected xenobiotics. In conclusion, reduced drug metabolism should be taken into account when evaluating the pharmacokinetics of drugs in patients with CRF.
Export Options
About this article
Cite this article as:
Pichette Vincent and Leblond A. Francois, Drug Metabolism in Chronic Renal Failure, Current Drug Metabolism 2003; 4 (2) . https://dx.doi.org/10.2174/1389200033489532
DOI https://dx.doi.org/10.2174/1389200033489532 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Metabolism-Mediated Xenobiotic Toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...read more
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...read more

- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Chitosan Formulations as Carriers for Therapeutic Proteins
Current Drug Discovery Technologies Leptin: The Prototypic Adipocytokine and its Role in NAFLD
Current Pharmaceutical Design Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention
Current Cancer Drug Targets Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers
Current Pharmaceutical Biotechnology Potential Role of Carbon Nanoparticles in Guiding Central Neck Dissection and Protecting Parathyroid Glands in Patients with Papillary Thyroid Cancer
Current Nanoscience The Safety and Efficacy of Parathyroid Hormone (PTH) as a Biological Response Modifier for the Enhancement of Bone Regeneration
Current Drug Safety Mechanisms for the Selective Actions of Vitamin D Analogues
Current Pharmaceutical Design Epigenetic Modification in Neuropathic Pain
Current Pharmaceutical Design The Role of Neuroendocrine Cells in Prostate Cancer: A Comprehensive Review of Current Literature and Subsequent Rationale to Broaden and Integrate Current Treatment Modalities
Current Medicinal Chemistry Retracted: Effects of Vitamin K2 on Osteoporosis
Current Pharmaceutical Design Extremity Exposure with <sup>99m</sup>Tc - Labelled Radiopharmaceuticals in Diagnostic Nuclear Medicine
Current Radiopharmaceuticals Recombinant Human Insulin-Like Growth Factor-1: A New Cardiovascular Disease Treatment Option?
Cardiovascular & Hematological Agents in Medicinal Chemistry Biologically Active Dietary Peptides
Mini-Reviews in Medicinal Chemistry Cyclin Dependent Kinase 1 Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Novel Biomarkers Assessing the Calcium Deposition in Coronary Artery Disease
Current Medicinal Chemistry Vitamin D and Metabolic Syndrome: Is There a Link?
Current Pharmaceutical Design Targeted Therapy Options for Treatment of Bone Metastases; Beyond Bisphosphonates
Current Pharmaceutical Design Menin, Histone H3 Methyltransferases, and Regulation of Cell Proliferation: Current Knowledge and Perspective
Current Molecular Medicine Microporation Techniques for Enhanced Delivery of Therapeutic Agents
Recent Patents on Drug Delivery & Formulation The Use of Intravenous Aminobisphosphonates for the Treatment of Pagets Disease of Bone
Mini-Reviews in Medicinal Chemistry