ArticleAntimicrobial agents and chemotherapy2017
Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity.
Article in Antimicrobial agents and chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Polymyxin antibiotics induce nephrotoxicity through the selective inhibition of Complex I-dependent respiration in mouse and rat mitochondria.Archives of toxicology · 2026Article
- Molecular mechanisms attributed to colistin renal proximal tubular epithelial cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Acute kidney injury of intravenous colistin sulfate compared with colistimethate sodium: a real-world, retrospective cohort study.BMC infectious diseases · 2025Article
- Factors Associated with Successful Treatment of Carbapenem-Resistant Gram-Negative Bacilli Infections Using Intravenous Colistin Sulfate in China: A Real-World Retrospective Study.Infection and drug resistance · 2025Article
- Polymyxin B in The Treatment of Infections Caused by Multidrug-Resistant Gram-Negative Bacteria in Children: A Retrospective Case Series and A Literature Review.Infection and drug resistance · 2025Article
- Evaluating nephrotoxicity reduction in a novel polymyxin B formulation: insights from a 3D kidney-on-a-chip model.Antimicrobial agents and chemotherapy · 2024Article
- Mechanisms of gelofusine protection in an in vitro model of polymyxin B-associated renal injury.American journal of physiology. Renal physiology · 2024Article
- Recent Advances in the Development of Polymyxin Antibiotics: 2010-2023.ACS infectious diseases · 2024Review
- Tobramycin Reduces Pulmonary Toxicity of Polymyxin B via Inhibiting the Megalin-Mediated Drug Uptake in the Human Lung Epithelial Cells.Pharmaceutics · 2024Article
- Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections.Frontiers in pharmacology · 2024Article
- Polymyxin B-Modified Fosfomycin Liposomes Target Gram-Negative Bacteria and Exert Synergistic Antibacterial Effect.ACS omega · 2023Article
- In vitro activity of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam alone or in combination with polymyxin B against carbapenem resistant Acinetobacter baumannii.The Journal of antibiotics · 2023Article
- Correlation between the drug concentration of polymyxin B and polymyxin B-associated acute kidney injury in critically ill patients: A prospective study.Pharmacology research & perspectives · 2022Article
- Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury.International journal of antimicrobial agents · 2022Article
- Polymyxin B-Associated Nephrotoxicity and Its Predictors: A Retrospective Study in Carbapenem-Resistant Gram-Negative Bacterial Infections.Frontiers in pharmacology · 2022Article
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- Polymyxin B-Induced Kidney Injury Assessment of a Novel Formulation of Polymyxin B (VRP-034) in Rats.Antibiotics (Basel, Switzerland) · 2021Article
- Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity.Drug design, development and therapy · 2021Article
- A Review of the Clinical Pharmacokinetics of Polymyxin B.Antibiotics (Basel, Switzerland) · 2019Review
- Structure-Function Studies of Polymyxin B Lipononapeptides.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite dose-limiting nephrotoxic potentials, polymyxin B has reemerged as the last line of therapy against multidrug-resistant Gram-negative bacterial infections. However, the handling of polymyxin B by the kidneys is still not thoroughly understood. The objectives of this study were to evaluate the impact of renal polymyxin B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225 to 250 g) were divided into three dosing groups, and polymyxin B was administered (5 mg/kg, 10 mg/kg, and 20 mg/kg) subcutaneously once daily. The onset of nephrotoxicity over 7 days and renal drug concentrations 24 h after the first dose were assessed. The effects of sodium maleate (400 mg/kg intraperitoneally) on megalin homeostasis were evaluated by determining the urinary megalin concentration and electron microscopic study of renal tissue. The serum/renal pharmacokinetics of polymyxin B were assessed in megalin-shedding rats. The onset of nephrotoxicity was correlated with the daily dose of polymyxin B. Renal polymyxin B concentrations were found to be 3.6 ± 0.4 μg/g, 9.9 ± 1.5 μg/g, and 21.7 ± 4.8 μg/g in the 5-mg/kg, 10-mg/kg, and 20-mg/kg dosing groups, respectively. In megalin-shedding rats, the serum pharmacokinetics of polymyxin B remained unchanged, but the renal exposure was attenuated by 40% compared to that of control rats. The onset of polymyxin B-induced nephrotoxicity is correlated with the renal drug exposure. In addition, megalin appears to play a pivotal role in the renal accumulation of polymyxin B, which might contribute to nephrotoxicity.
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