ArticleJournal of pharmaceutical sciences2011
Effects of uremic toxins on transport and metabolism of different biopharmaceutics drug disposition classification system xenobiotics.
Article in Journal of pharmaceutical sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Review
- Clinical Pharmacokinetic-Pharmacodynamic Relationships of Pharmacological Strategies for Attenuating p-Cresyl Sulfate in Patients with Kidney Disease.Clinical pharmacokinetics · 2025Article
- Changes in Protein Expression of Renal Drug Transporters and Drug-Metabolizing Enzymes in Autosomal Dominant Polycystic Kidney Disease Patients.Clinical pharmacology and therapeutics · 2025Article
- Chloramine Disinfection of Levofloxacin and Sulfaphenazole: Unraveling Novel Disinfection Byproducts and Elucidating Formation Mechanisms for an Enhanced Understanding of Water Treatment.Molecules (Basel, Switzerland) · 2024Article
- Article
- Significant Correlations between p-Cresol Sulfate and Mycophenolic Acid Plasma Concentrations in Adult Kidney Transplant Recipients.Clinical drug investigation · 2022Observational
- Nanostructured Valsartan Microparticles with Enhanced Bioavailability Produced by High-Throughput Electrohydrodynamic Room-Temperature Atomization.Molecular pharmaceutics · 2021Article
- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion.Toxins · 2020Article
- Uremic serum residue decreases SN-38 sensitivity through suppression of organic anion transporter polypeptide 2B1 in LS-180 colon cancer cells.Scientific reports · 2019Article
- Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease.Toxins · 2019Review
- Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2018Article
- Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.Expert review of clinical pharmacology · 2018Review
- Analyzing and interpreting genome data at the network level with ConsensusPathDB.Nature protocols · 2016Article
- BDDCS, the Rule of 5 and drugability.Advanced drug delivery reviews · 2016Review
- Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters.Clinical journal of the American Society of Nephrology : CJASN · 2015Article
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- Effects of chronic kidney disease on liver transport: quantitative intravital microscopy of fluorescein transport in the rat liver.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Article
- Consequences of renal failure on non-renal clearance of drugs.Clinical pharmacokinetics · 2014Review
- Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug.BMC nephrology · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Chronic kidney disease (CKD) is recognized to cause pharmacokinetic changes in renally excreted drugs; however, pharmacokinetic changes are also reported for drugs that are nonrenally eliminated. Few studies have investigated how uremic toxins may affect drug transporters and metabolizing enzymes and how these may result in pharmacokinetic/metabolic changes in CKD. Here, we investigated the effects of uremic toxins and human uremic serum on the transport of the prototypical transporter substrate [(3) H]-estrone sulfate and three Biopharmaceutics Drug Disposition Classification System (BDDCS) drugs, propranolol, losartan, and eprosartan. We observed a significant decrease in [(3) H]-estrone sulfate, losartan, and eprosartan uptake with some uremic toxins in both transfected cells and rat hepatocytes. The uptake of losartan was decreased in rat and human hepatocytes (28% and 48%, respectively) in the presence of hemodialysis (HD) serum. Time-course studies of losartan showed a 27%, 65%, and 68% increase in area under the curve (AUC) in the presence of HD serum, rifampin, and sulfaphenazole, respectively. Intracellular losartan AUC decreased significantly in the treatment groups, and the metabolite AUC decreased by 41% and 26% in rifampin- and sulfaphenazole-treated group, respectively. The intracellular AUC of eprosartan increased 190% in the presence of HD serum. These studies indicate that the uremic toxins contained in HD serum play an important role in drug disposition through drug transporters, and that there would be differential effects depending on the BDDCS classification of the drug.
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