The population pharmacokinetics and dose optimization of polymyxin B in critically ill patients with or without extracorporeal membrane oxygenation

Abstract

What is known and objective: The presence of extracorporeal membrane oxygenation (ECMO) is suggested to further exacerbate the pharmacokinetics (PK) alterations that occur during critical illness. The objectives of this study were to determine the population PK model of polymyxin B in critically ill patients with or without ECMO support investigated the influence of ECMO on PK variability and to identify an optimal dosing strategy.Methods: Forty-four critically ill patients were enrolled, including eight patients with ECMO support. Eight serial serum samples were collected from each patient at steady state. The population PK was determined using NONMEM and Monte Carlo simulation was performed to evaluate the exposures of different dosing regimens. Results:The PK analyses included 342 steady-state concentrations and a twocompartment model was optimal for polymyxin B PK data modelling. In the final model, creatinine clearance (CL CR ) was the significant covariate on CL (typical value 1.27 L/h; between-subject variability 15.1%) and ECMO did not show a significant impact on the polymyxin B PK. Additionally, we found that the PK parameter estimates of patients with and without ECMO support were mostly similar. Based on Monte Carlo simulations, the dose escalation of polymyxin B in patients with increased CL CR improved the probability of achieving required exposure. For patients with CL CR ≤ 120 ml/min, a dosage regimen of 100 mg every 12 h may represent the optimal regimen at an MIC of 1 mg/L.What is new and conclusion: The impact of ECMO on the polymyxin B PK is likely to be minimal. Our study showed a potential relationship between CL CR and polymyxin B CL, and the dose of polymyxin B should be adjusted in patients with increased CL CR .

Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial

“…Interestingly, a higher proportion of patients reached the ssAUC 0-24 standard of 50–100 mg ·h/L in the septic shock subgroup compared to the total group. Hence, we compared some baseline characteristics between sepsis patients with and without shock to explain why target AUC compliance rates were high in more severe patients, and the results showed that the level of Scr was significantly higher in patients with septic shock and the plasma concentration of polymyxin B appeared to increase with increasing Scr; a similar phenomenon was described in previous studies [ 22 , 23 ].…”