Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analysed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (%
f
T
>MIC
) and toxic exposures of greater than 360 mg/L. Tazobactam target of percentage time free concentrations >2 mg/L was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models with body mass index, creatinine clearance and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5 g 6-hourly regimen administered over 4-hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/L while exposing patients to a <3% probability of toxic concentrations. In patients receiving ECMO and RRT a frequency reduction to 12-hourly dosing reduces the probability of toxic concentrations, although this remains at 7 – 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.
Population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor types and model-informed dosing strategy
