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

doi:10.1128/AAC.02300-19

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

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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 language	English (US)
Article number	e02300-19
Journal	Antimicrobial Agents and Chemotherapy
Volume	64
Issue number	5
DOIs	https://doi.org/10.1128/AAC.02300-19
State	Published - 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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Liu, J., Pais, G. M., Avedissian, S. N., Gilchrist, A., Lee, A., Rhodes, N. J., Hauser, A. R., & Scheetz, M. H. (2020). Evaluation of dose-fractionated polymyxin B on acute kidney injury using a translational in vivo rat model. Antimicrobial Agents and Chemotherapy, 64(5), [e02300-19]. https://doi.org/10.1128/AAC.02300-19

Evaluation of dose-fractionated polymyxin B on acute kidney injury using a translational in vivo rat model. / Liu, Jiajun; Pais, Gwendolyn M.; Avedissian, Sean N.; Gilchrist, Annette; Lee, Andrew; Rhodes, Nathaniel J.; Hauser, Alan R.; Scheetz, Marc H.

In: Antimicrobial Agents and Chemotherapy, Vol. 64, No. 5, e02300-19, 01.05.2020.

Research output: Contribution to journal › Article

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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.",

keywords = "Acute kidney injury, Animal model, Colistin, Pharmacodynamic, Pharmacokinetic, Polymyxin B, Polymyxins, Toxicodynamic, Urinary biomarker",

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