Population Pharmacokinetics and Dosing Regimen Optimization of Piperacillin in Critically Ill Patients

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 ChinaCorrespondence: 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.comPurpose: 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