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已发表论文
重症患者哌拉西林群体药代动力学和给药方案优化
Authors Dong Z, Shi H, Yang Y, Yi Q, Jiang Z, Li Y
Received 3 July 2025
Accepted for publication 23 December 2025
Published 13 January 2026 Volume 2026:20 551307
DOI https://doi.org/10.2147/DDDT.S551307
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Leonidas Panos
Zhonghua Dong,1 Haiyan Shi,1 Yilei Yang,1 Qiaoyan Yi,1 Zhiming Jiang,2 Yan Li1
1Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, People’s Republic of China
Correspondence: Zhiming Jiang, Department of Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, 16766 Jingshi Road, Jinan, 250014, People’s Republic of China, Email jiang7708@sina.com Yan Li, Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Jinan, 250014, People’s Republic of China, Email Li_xyan@126.com
Purpose: Critically ill patients exhibit significant pharmacokinetic alterations, necessitating population pharmacokinetic (PPK) modeling of piperacillin to optimize dosing regimens. This study aimed to develop a PPK model for piperacillin in critically ill patients from China and optimize dosing regimens based on model predictions.
Patients and Methods: A nonlinear mixed-effects modeling approach was applied to characterize piperacillin pharmacokinetics. Covariate analysis identified significant predictors of CL and V. Monte Carlo simulations assessed dosing regimens against pharmacodynamic targets.
Results: The final model estimated population typical CL and V as 6.48 L/h and 19 L, respectively. Estimated glomerular filtration rate and body weight significantly influenced CL, while plasma albumin affected V. Simulations revealed that continuous intravenous infusion achieved higher probability of target attainment (PTA) than intermittent dosing, particularly for pathogens with elevated MICs. Obesity and augmented renal clearance reduced PTA, necessitating dose escalation or more frequent administration.
Conclusion: This study highlights the interplay between host pathophysiology, pathogen susceptibility, and drug exposure. Guided by the PPK model and susceptibility testing, tailored dosing strategies are crucial for optimizing therapeutic outcomes in critical populations.
Keywords: piperacillin, population pharmacokinetic, critically ill patient, antimicrobial
1Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, People’s Republic of China
Correspondence: Zhiming Jiang, Department of Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, 16766 Jingshi Road, Jinan, 250014, People’s Republic of China, Email jiang7708@sina.com Yan Li, Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Jinan, 250014, People’s Republic of China, Email Li_xyan@126.com
Purpose: Critically ill patients exhibit significant pharmacokinetic alterations, necessitating population pharmacokinetic (PPK) modeling of piperacillin to optimize dosing regimens. This study aimed to develop a PPK model for piperacillin in critically ill patients from China and optimize dosing regimens based on model predictions.
Patients and Methods: A nonlinear mixed-effects modeling approach was applied to characterize piperacillin pharmacokinetics. Covariate analysis identified significant predictors of CL and V. Monte Carlo simulations assessed dosing regimens against pharmacodynamic targets.
Results: The final model estimated population typical CL and V as 6.48 L/h and 19 L, respectively. Estimated glomerular filtration rate and body weight significantly influenced CL, while plasma albumin affected V. Simulations revealed that continuous intravenous infusion achieved higher probability of target attainment (PTA) than intermittent dosing, particularly for pathogens with elevated MICs. Obesity and augmented renal clearance reduced PTA, necessitating dose escalation or more frequent administration.
Conclusion: This study highlights the interplay between host pathophysiology, pathogen susceptibility, and drug exposure. Guided by the PPK model and susceptibility testing, tailored dosing strategies are crucial for optimizing therapeutic outcomes in critical populations.
Keywords: piperacillin, population pharmacokinetic, critically ill patient, antimicrobial