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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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 › peer-review

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

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",

author = "Jiajun Liu and Pais, {Gwendolyn M.} and Avedissian, {Sean N.} and Annette Gilchrist and Andrew Lee and Rhodes, {Nathaniel J.} and Hauser, {Alan R.} and Scheetz, {Marc H.}",

note = "Funding Information: This study was supported in part by a grant (LEE17GO) awarded from the Cystic Fibrosis Foundation (CFF). The funding agency had no role in study design, data collection and interpretation, or the decision to submit the work for publication. We thank the Midwestern University CORE for use and access to the liquid chromatography-tandem mass spectrometer (LC-MS/MS).",

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AU - Lee, Andrew

AU - Rhodes, Nathaniel J.

AU - Hauser, Alan R.

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N1 - Funding Information: This study was supported in part by a grant (LEE17GO) awarded from the Cystic Fibrosis Foundation (CFF). The funding agency had no role in study design, data collection and interpretation, or the decision to submit the work for publication. We thank the Midwestern University CORE for use and access to the liquid chromatography-tandem mass spectrometer (LC-MS/MS).

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