A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

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Tác giả: Michael Cohen-Wolkowiez, Pieter J Colin, Pieter A J G De Cock, Jan J De Waele, Sofie A M Dhaese, Douglas J Eleveld, Timothy W Felton, Sutep Jaruratanasirikul, Daming Kong, Jeroen V Koomen, Jeffrey Lipman, Robin Michelet, Jason A Roberts, Fekade B Sime, Michel M R F Struys, Fabio Silvio Taccone, Céline Thibault, Danny Tsai, Andrew A Udy

Ngôn ngữ: eng

Ký hiệu phân loại: 920.71 Men

Thông tin xuất bản: Switzerland : Clinical pharmacokinetics , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 216568

BACKGROUND AND OBJECTIVES: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f METHODS: Population PK models were separately built for PIP and TAZ based on data from 13 studies in various patient populations. In the development of those single-drug models, postnatal age (PNA), postmenstrual age (PMA), total body weight (TBW), height, and serum creatinine (SCR) were tested as covariates. Subsequently, a combined population PK model was established and the correlations between the PK of PIP and TAZ were tested. Monte Carlo simulations were performed based on the final combined model to evaluate the current dosing recommendations. RESULTS: The final combined model for PIP/TAZ consisted of four compartments (two for each drug), with covariates including TBW, PMA, and SCR. For a 70-kg, 35-year-old patient with SCR of 0.83 mg L CONCLUSIONS: We developed a combined population PK model for PIP/TAZ across a broad range of patients covering the extremes of patient characteristics. This model can be used as a robust a priori model for Bayesian forecasting to achieve individualised dosing. The simulations indicate that adjustments based on the allometric theory as well as maturation and decline of CL of PIP may help the current dosing recommendations to provide consistent target attainment across patient populations.
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