Evaluation of dose-fractionated polymyxin B on acute kidney injury using a translational in vivo rat model

Jiajun Liu, Gwendolyn M. Pais, Sean N. Avedissian, Annette Gilchrist, Andrew Lee, Nathaniel J. Rhodes, Alan R. Hauser, Marc H. Scheetz

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated dose-fractionated polymyxin B (PB) on acute kidney injury (AKI). PB at 12 mg of drug/kg of body weight per day (once, twice, and thrice daily) was administered in rats over 72 h. The thrice-daily group demonstrated the highest KIM-1 increase (P=0.018) versus that of the controls (P=0.99) and histopathological damage (P=0.013). A three-compartment model best described the data (bias, 0.129 mg/liter; imprecision, 0.729 mg2/liter2; R2, 0.652,). Area under the concentration-time curve at 24 h (AUC24) values were similar (P=0.87). The thricedaily dosing scheme resulted in the most PB-associated AKI in a rat model.

Original languageEnglish (US)
Article numbere02300-19
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number5
DOIs
StatePublished - May 1 2020

Keywords

  • Acute kidney injury
  • Animal model
  • Colistin
  • Pharmacodynamic
  • Pharmacokinetic
  • Polymyxin B
  • Polymyxins
  • Toxicodynamic
  • Urinary biomarker

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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