Population pharmacokinetics of piperacillin in non-critically Ill hospitalized patients: A study from Pakistan

Background: Piperacillin/tazobactam is commonly used for the treatment of severe infections in hospitalized patients. While its pharmacokinetics have been extensively studied in critically ill patients, data on non-critically ill hospitalized patients remain limited. Objectives: This study aimed to characterize the population pharmacokinetics of piperacillin in non-critically ill Pakistani patients and to identify significant covariates influencing drug disposition. Methods: This prospective, single-center study was conducted at Ayub Teaching Hospital. Serial plasma samples were collected at multiple post-dose time points to quantify piperacillin concentrations using high-performance liquid chromatography. Demographic, clinical and laboratory data were systematically recorded. Population pharmacokinetic modeling was performed using Monolix 2024R1 and model selection was guided by standard diagnostic criteria, the Akaike Information Criterion and objective function values. Results: Twenty-five non-critically ill patients (median age: 54 years) were enrolled. The pharmacokinetic profile of piperacillin was adequately described by a two-compartment model with first-order elimination. The estimated glomerular filtration rate by the CKD-EPI 2021 equation, significantly influenced clearance, which was estimated at 15.58 L/h. The central volume of distribution was 27.06 L, the peripheral volume of distribution was 4.48 L and the intercompartmental clearance rate was 4.16 L/h. Conclusion: Piperacillin pharmacokinetics in non-critically ill patients are primarily influenced by renal function, with the CKD-EPI 2021 equation providing the most reliable estimates of clearance. Despite the limited sample size, these findings provide a foundation for future individualized and model-informed precision dosing approaches, particularly in Pakistan.