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已发表论文
危重患者多黏菌素 B 群体药代动力学的多中心研究
Authors Wang Y, Wang X, Lei L, Sun W, Wu Z, Lan J , Chen J, Wang Y, Yao F, Hu L , Bai Y, Chen C
Received 7 February 2025
Accepted for publication 15 January 2026
Published 3 February 2026 Volume 2026:20 521070
DOI https://doi.org/10.2147/DDDT.S521070
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Georgios Panos
Yirong Wang,1,2,* Xipei Wang,3,4,* Liming Lei,5,6,* Wanheng Sun,7,* Zheng Wu,2 Jinhua Lan,8 Jingchun Chen,2 Yifan Wang,1 Fen Yao,1 Linhui Hu,9 Yunpeng Bai,10 Chunbo Chen1
1Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 3Research Center of Medical Sciences, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 6Laboratory of South China Structural Heart Disease, Guangzhou, People’s Republic of China; 7Department of Neurology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 8Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, People’s Republic of China; 9Department of Critical Care Medicine, Maoming People’s Hospital, Maoming, People’s Republic of China; 10Department of Pharmacy, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chunbo Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China, Email gghccm@163.com
Purpose: To develop a population pharmacokinetics (PPK) model for polymyxin B (PB) in critically ill patients, and propose individualized dosing regimens.
Methods: Blood samples were collected from intensive care unit (ICU) patients after the third or subsequent PB doses. The NONMEM software was used to construct a PPK model, with a focus on identifying key covariates influencing drug behavior. Patient-specific dosing strategies and probability of target attainment (PTA) were evaluated using Monte Carlo simulations.
Results: A total of 56 ICU patients with 350 blood samples were included. A two-compartment model best described the data, with estimated glomerular filtration rate (eGFR) identified as a significant covariate on clearance (CL). The value of CL was 1.68 L/h. The estimated central compartment volume (V1) was 14.3 L, the peripheral compartment volume (V2) was 48.84 L, and the inter-compartmental clearance (Q) was 4.67 L/h. The simulation results demonstrated a positive correlation between probability of target attainment (PTA) and maintenance dose (MD) at a fixed first dose (FD) for any given minimum inhibitory concentration (MIC). Conversely, a similar increase in PTA with higher FD was observed when MD was held constant. Furthermore, achieving therapeutic targets required larger dosing regimens in patients with better renal function.
Conclusion: PB clearance is influenced by eGFR in critically ill patients. Higher MIC values or preserved renal function necessitate increased dosing. This study provides tailored dosing recommendations for ICU patients based on renal function and MIC.
Keywords: polymyxin B, population pharmacokinetics, renal function, ICU, dosage regimen
1Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 3Research Center of Medical Sciences, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 6Laboratory of South China Structural Heart Disease, Guangzhou, People’s Republic of China; 7Department of Neurology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 8Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, People’s Republic of China; 9Department of Critical Care Medicine, Maoming People’s Hospital, Maoming, People’s Republic of China; 10Department of Pharmacy, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chunbo Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China, Email gghccm@163.com
Purpose: To develop a population pharmacokinetics (PPK) model for polymyxin B (PB) in critically ill patients, and propose individualized dosing regimens.
Methods: Blood samples were collected from intensive care unit (ICU) patients after the third or subsequent PB doses. The NONMEM software was used to construct a PPK model, with a focus on identifying key covariates influencing drug behavior. Patient-specific dosing strategies and probability of target attainment (PTA) were evaluated using Monte Carlo simulations.
Results: A total of 56 ICU patients with 350 blood samples were included. A two-compartment model best described the data, with estimated glomerular filtration rate (eGFR) identified as a significant covariate on clearance (CL). The value of CL was 1.68 L/h. The estimated central compartment volume (V1) was 14.3 L, the peripheral compartment volume (V2) was 48.84 L, and the inter-compartmental clearance (Q) was 4.67 L/h. The simulation results demonstrated a positive correlation between probability of target attainment (PTA) and maintenance dose (MD) at a fixed first dose (FD) for any given minimum inhibitory concentration (MIC). Conversely, a similar increase in PTA with higher FD was observed when MD was held constant. Furthermore, achieving therapeutic targets required larger dosing regimens in patients with better renal function.
Conclusion: PB clearance is influenced by eGFR in critically ill patients. Higher MIC values or preserved renal function necessitate increased dosing. This study provides tailored dosing recommendations for ICU patients based on renal function and MIC.
Keywords: polymyxin B, population pharmacokinetics, renal function, ICU, dosage regimen