ArticleBritish journal of pharmacology2005
Effects of serum from patients with chronic renal failure on rat hepatic cytochrome P450.
Article in British journal of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Complex Drug-Drug-Gene-Disease Interactions Involving Cytochromes P450: Systematic Review of Published Case Reports and Clinical Perspectives.Clinical pharmacokinetics · 2018Pooled it
- Using midazolam to monitor changes in hepatic drug metabolism in critically ill patients.Intensive care medicine · 2009Trial
- Pharmacokinetics of mycophenolic acid in patients with lupus nephritis.Pharmacotherapy · 2009Trial
- Metoprolol Population Pharmacokinetics in Older Chinese Patients With CKM Syndrome: Joint Effects of rs1065852 and CKMClinical and translational science · 2026Article
- Pharmacokinetics and Safety of Fezolinetant in Women with Hepatic or Renal Impairment.Journal of clinical pharmacology · 2025Article
- The impact of progressive chronic kidney disease on hepatic drug metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- The Impact of Suboptimal 25-Hydroxyvitamin D Levels and Cholecalciferol Replacement on the Pharmacokinetics of Oral Midazolam in Control Subjects and Patients With Chronic Kidney Disease.Journal of clinical pharmacology · 2022Article
- Use of Physiologically Based Pharmacokinetic Modeling to Evaluate the Impact of Chronic Kidney Disease on CYP3A4-Mediated Metabolism of Saxagliptin.Journal of clinical pharmacology · 2022Article
- Drug-Dosing Adjustment in Dogs and Cats with Chronic Kidney Disease.Animals : an open access journal from MDPI · 2022Review
- Population Pharmacokinetic Model-Based Evaluation of Intact Oxaliplatin in Rats with Acute Kidney Injury.Cancers · 2021Article
- Advanced oxidation protein products downregulate CYP1A2 and CYP3A4 expression and activity via the NF-κB-mediated signaling pathway in vitro and in vivo.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Influence of vitamin D treatment on functional expression of drug disposition pathways in human kidney proximal tubule cells during simulated uremia.Xenobiotica; the fate of foreign compounds in biological systems · 2021Article
- Drug-drug interactions in polypharmacy patients: The impact of renal impairment.Current research in pharmacology and drug discovery · 2021Review
- Vitamin D Metabolism and Its Role in Mineral and Bone Disorders in Chronic Kidney Disease in Humans, Dogs and Cats.Metabolites · 2020Review
- End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s.Pharmacological reports : PR · 2020Article
- The effect of chronic kidney disease on CYP2B expression and activity in male Wistar rats.Pharmacology research & perspectives · 2019Article
- Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease.Toxins · 2019Review
- Effects of Renal Function on Crizotinib Pharmacokinetics: Dose Recommendations for Patients with ALK-Positive Non-Small Cell Lung Cancer.Clinical drug investigation · 2017Article
- Secondary Hyperparthyroidism: Pathogenesis, Diagnosis, Preventive and Therapeutic Strategies.Reviews in endocrine & metabolic disorders · 2017Review
- Influence of chronic kidney disease and haemodialysis treatment on pharmacokinetics of nebivolol enantiomers.British journal of clinical pharmacology · 2016Article
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Authors and funding
7 authors.
Funding
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Abstract
1. In humans, chronic renal failure (CRF) is associated with decreased hepatic drug metabolism, particularly that mediated by the cytochrome P450 (P450). The mechanisms remain poorly understood. The present study aimed to investigate the effects of the serum of patients with CRF on liver P450, and to evaluate whether renal replacement therapies (dialysis or transplantation) impede the inhibition of CRF serum on P450. 2. Rat hepatocytes were incubated for 24 h with serum from patients with severe CRF and from controls to measure (1) P450 level, (2) protein expression and mRNA levels of P450 isoforms and (3) metabolic activities of CYP3A and CYP1A. Similar experiments were performed with serum of patients once on chronic hemodialysis and after kidney transplantation. 3. In rat hepatocytes incubated for 24 h with serum from patients with CRF, P450 level and protein expression, as well as mRNA levels of P450 isoforms (CYP1A2, 2C6, 2C11, 2D1/2D2, 3A2 and 4A1/4A3), were decreased by more than 45% (P<0.001) compared to control serum, while the levels of CYP2E1 were not modified. CYP3A and CYP1A activities were decreased by 51 and 59% (P<0.001), respectively. The inhibitory effect of serum obtained from patients before first dialysis was similar after 1 or 6 months on chronic hemodialysis but was lost after successful kidney transplantation. In CRF serum, the fraction containing proteins between 10 and 15 kDa decreases P450. 4. Human uremic serum contains mediator(s) that decreases rat hepatic P450 activity and expression secondary to reduced gene expression. The inhibitory effect of serum persists even after initiation of dialysis, but disappears after normalization of renal function following kidney transplantation.
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