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\begin{document}

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



\author[1]{Qinghua Ye}%
\author[2]{Qianlin Wang}%
\author[2]{WenQian Chen}%
\author[2]{Ruihao Zhang}%
\author[2]{Ziying Chen}%
\author[1]{Pengmei Li}%
\author[1]{Xianglin Zhang}%
\author[2]{Qingyuan Zhan}%
\author[2]{Chen Wang}%
\affil[1]{China-Japan Friendship Hospital}%
\affil[2]{Affiliation not available}%


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  \date{May 26, 2024}


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\begin{abstract}
Aims: The objectives of this study were to determine the population
pharmacokinetics (PK) model of polymyxin B in critically ill patients
with or without extracorporeal membrane oxygenation (ECMO) support that
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
two-compartment model was optimal for polymyxin B PK data modelling. In
the final model, creatinine clearance (CLCR) 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 CLCR improved the probability of achieving required exposure.
For patients with CLCR[?]120 mL/min, a dosage regimen of 100mg every 12h
may represent the optimal regimen at an MIC of 1 mg/L. Conclusion: The
impact of ECMO on the polymyxin B PK is likely to be minimal. Our study
showed a potential relationship between CLCR and polymyxin B CL, and the
dose of polymyxin B should be adjusted in patients with increased CLCR.%
\end{abstract}%



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