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 thrice-daily dosing scheme resulted in the most PB-associated AKI in a rat model.
Highlights
We investigated dose-fractionated polymyxin B (PB) on acute kidney injury (AKI)
Male Sprague-Dawley rats were divided into three experimental groups (Fig. 1) as follows: once daily (QD), twice daily (BID), and thrice daily (TID) and received subcutaneous clinical grade PB
Best fit models were selected according to Ϫ2 log-likelihood (Ϫ2LL), Akaike’s information criterion (AIC), and rule of parsimony
Summary
Evaluation of Dose-Fractionated Polymyxin B on Acute Kidney Injury Using a Translational In Vivo Rat Model. Avedissian,d,e Annette Gilchrist,a,b,f Andrew Lee,g Nathaniel J. Scheetza,b,c aMidwestern University, Downers Grove, Illinois, USA bMidwestern University, Chicago College of Pharmacy Pharmacometrics Center of Excellence, Downers Grove, Illinois, USA cNorthwestern Memorial Hospital, Chicago, Illinois, USA dAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC), Center for Drug Discovery, Omaha, Nebraska, USA eUniversity of Nebraska Medical Center, College of Pharmacy, Omaha, Nebraska, USA fNorthwestern University, Chicago, Illinois, USA gDepartment of Chemical & Biological Engineering, Northwestern University, Evanston, Illinois, USA
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