Population Pharmacokinetics and Dosing Optimization of Piperacillin in Elderly Patients with Pneumonia in the Intensive Care Unit

Jing Sun, Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Chuang Yang, Department of Intensive Care, The Second Hospital of Shandong University, Jinan, China.
Bo-Hao Tang, Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Guo-Xiang Hao, Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
John van den Anker, Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.
Yue-E Wu, Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
De-Qing Sun, Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
Yi Zheng, Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Wei Zhao, Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Document Type

Journal Article

Publication Date

8-5-2025

Journal

Journal of clinical pharmacology

DOI

10.1002/jcph.70089

Keywords

Monte Carlo simulation; elderly; piperacillin; pneumonia; population pharmacokinetics

Abstract

Piperacillin/tazobactam is the first-line treatment for pneumonia in elderly patients. However, there are differences in dosing regimens and infusion times among different centers. We aimed to evaluate the population pharmacokinetics of piperacillin in elderly patients with pneumonia and optimize the dosing regimens. This was a prospective pharmacokinetic (PK) study of piperacillin/tazobactam in elderly patients with pneumonia using an opportunistic sampling design. The blood concentration of piperacillin was determined by high-performance liquid chromatography. A population PK model was constructed using NONMEM software, and its predictive performance was further validated in a separate test cohort. The final population PK model was used for dose optimization. A total of 151 blood samples from 73 patients were used to develop a population PK model, and 60 concentrations of therapeutic drug monitoring from 22 patients were used for model validation. A one-compartment model with first-order elimination was established. Covariate analysis showed that eGFR was the only covariate. Monte Carlo simulation results showed that for pathogens with MIC values of 8 and 16 mg/L, the dosing regimen (4000 mg every 6/8 h administered 30 min) used in this study resulted in PTAs of 23.5%-64.3%. The PTAs of the dosing regimen 4000 mg every 6 h administered by 4-h infusion for patients with different levels of renal function exceeded 90% (90.7%-99.8%), except for patients with eGFR ≥ 50 mL/min/1.73 m.

Department

Pediatrics

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