Comparing the Population Pharmacokinetics of and Acute Kidney Injury Due to Polymyxin B in Chinese Patients with or without Renal Insufficiency

Abstract

ABSTRACT Despite excellent bactericidal effect, dosing adjustment of polymyxin B for patients with renal insufficiency and polymyxin B-related nephrotoxicity is still a major concern to clinicians. The aim of this study was to compare the population pharmacokinetics (PK) properties of polymyxin B in Chinese patients with different renal functions and to investigate the relationship between PK parameters and polymyxin B-related acute kidney injury (AKI). A total of 37 patients with normal renal function (creatinine clearance ≥ 80 ml/min) and 33 with renal insufficiency (creatinine clearance < 80 ml/min) were included. In the two-compartment population PK models, the central compartment clearance (CL) (2.19 liters/h versus 1.58 liters/h; P < 0.001) and intercompartmental clearance (Q) (13.83 liters/h versus 10.28 liters/h; P < 0.001) values were significantly different between the two groups. The simulated values for AUC across 24 h at steady state (AUCss,24h) for patients with normal renal function were higher than those for patients with renal insufficiency. However, renal dosing adjustment of polymyxin B seemed not to be necessary. In addition, during the treatment, AKI occurred in 23 (32.86%) patients. The polymyxin B AUCss,24h in patients with AKI was significantly higher than that in patients without AKI (108.66 ± 70.10 mg · h/liter versus 66.18 ± 34.79 mg · h/liter; P = 0.001). Both the receiver operating characteristic (ROC) curve and logistic regression analysis showed that an AUCss,24h of >100 mg · h/liter was a good predictor for the probability of nephrotoxicity.