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

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 m².