Mid ‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

This study aimed to evaluate the association between polymyxin B (PMB) exposure and acute kidney injury (AKI) and analyze the risk factors for PMB-induced AKI in critically ill patients. Plasma concentrations of PMB were determined using an ultra-performance liquid chromatography-tandem mass spectrometer in intensive care unit patients who were administered PMB. Univariate and multivariate analyses were conducted to identify risk factors. A receiver operating characteristic curve was constructed to assess the discriminant power of the factors and to identify the cut-off value for AKI. The white blood cell count and estimated area under the concentration –time curve (AUC) of patients administered PMB were independent risk factors for PMB-induced AKI, where AUC were calculated using a first-order pharmacokinetic equation based on the mid-dosing interval concentration (C1/2t) and peak concentration. The area under the receiver operating characteristic curve of the final model was 0.805 (95% confidence interval 0.690 –0.921). The cut-off value for the combined predictor was 0.57. Alternatively, when using C1/2t, which was strongly correlated with AUC, as the only independent risk factor, the analysis showed that the 3.47 μg/mL threshold provides favorable differentiation between the AKI and non-AKI groups. These results provide insightful information for TDM-guiding PMB dosing in the clinical practice.
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research