Evaluation Of Individualized Cefepime Dosing Strategy Using Population Pharmacokinetics

2021 ◽  
Author(s):  
Yoonsun Mo ◽  
Natalia Shcherbakova ◽  
Kelsey L. Inman ◽  
Wai Kin Li ◽  
Kateryna Kovalenko ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Dosing Strategy

Population pharmacokinetics of piperacillin and tazobactam in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

2021 ◽  
Author(s):  
Vesa Cheng ◽  
Mohd H. Abdul-Aziz ◽  
Fay Burrows ◽  
Hergen Buscher ◽  
Young-Jae Cho ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Plasma Concentrations ◽  
Membrane Oxygenation ◽  
Optimal Dosing ◽  
Patient Groups ◽  
Dosing Strategy ◽  
Toxic Concentrations ◽  
Staged Testing

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.

scholarly journals Population Pharmacokinetics of an Anti-PD-1 Antibody Camrelizumab in Patients with Multiple tumor types and model informed dosing strategy

2020 ◽  
Author(s):  
Chen-yu Wang ◽  
Chang-cheng Sheng ◽  
Guang-li Ma ◽  
Da Xu ◽  
Xiao-qin Liu ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Model Building ◽  
Compartment Model ◽  
Patient Characteristics ◽  
Multiple Tumor ◽  
Mixed Effects Modeling ◽  
Flat Dose ◽  
Dosing Strategy ◽  
Tumor Types ◽  
The Impact

AbstractObjectiveCamrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of relapsed or refractory classical Hodgkin lymphoma. The aim of this study was to perform a population pharmacokinetics (PK) analysis of camrelizumab to quantify the impact of patient characteristics on PK and to investigate the appropriateness of flat dose in the dosing regimen.MethodsA total of 3298 camrelizumab concentrations from 133 patients from four studies were analyzed using nonlinear mixed effects modeling. Covariate model building was conducted using stepwise forward addition and backward elimination. Monte Carlo simulation was conducted to compare exposures of 200 mg and 3 mg/kg every 2-week regimens.ResultsThe PK of camrelizumab were adequately described by a two-compartment model with parallel linear and nonlinear clearances. Baseline albumin had significant effects on linear clearance, and weight had effects on inter-compartmental clearance. Moreover, 200 mg and 3 mg/kg regimens provide similar exposure distributions with no advantage to either dosing approach.ConclusionPopulation PK analysis provided an integrated evaluation of the impact of albumin and weight on the PK of camrelizumab. It also provided evidence that neither the flat-dose nor the weight-based dose regimen was advantageous over the other for most patients with tumors.

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