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Population Pharmacokinetics of the Piperacillin Component of Piperacillin/Tazobactam in Pediatric Oncology Patients With Fever and Neutropenia
Journal article   Peer reviewed

Population Pharmacokinetics of the Piperacillin Component of Piperacillin/Tazobactam in Pediatric Oncology Patients With Fever and Neutropenia

Jeffrey J. Cies, Jaimi Jain and Joseph L. Kuti
Pediatric blood & cancer, v 62(3), pp 477-482
01 Mar 2015
PMID: 25328131

Abstract

Hematology Life Sciences & Biomedicine Oncology Pediatrics Science & Technology
BackgroundTo describe the population pharmacokinetics of the piperacillin component of piperacillin/tazobactam. ProcedureThis pharmacokinetic study included 21 pediatric (age 3-10 years) patients receiving piperacillin/tazobactam to treat fever with neutropenia. Each patient contributed 1-3 blood samples for piperacillin concentration determination. Population pharmacokinetic analyses were conducted using Pmetrics software. A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for multiple dosing regimens, using 50% of free drug time above the minimum inhibitory concentration (MIC) as the primary pharmacodynamic threshold. ResultsMeanSD body weight was 28.5 +/- 9.7kg. Piperacillin concentration data best fit a two-compartment model with linear clearance, using total body weight as a covariate for clearance (CL) and volume of the central compartment (Vc). Population estimates for CL, Vc, and intercompartment transfer constants were 0.204 +/- 0.076L/h/kg, 0.199 +/- 0.107L/kg, 0.897 +/- 1.050h(-1), and 1.427 +/- 1.609h(-1), respectively. R-2, bias, and precision for the Bayesian fit were 0.998, -0.032, and 2.2 mu g/ml, respectively. At the MIC breakpoint of 16 mu g/ml for Pseudomonas aeruginosa, PTAs for 50mg/kg q4h as a 0.5hr infusion was 93.9%; for 100mg/kg q8h as 0.5 and 4hr infusion: 64.6% and 100%; for 100mg/kg q6h as 0.5 and 3hr infusion: 86.5% and 100%; and for 400mg/kg continuous infusion: 100%, respectively. ConclusionsIn children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure. Pediatr Blood Cancer 2015;62:477-482. (c) 2014 Wiley Periodicals, Inc.

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Collaboration types
Domestic collaboration
Web of Science research areas
Hematology
Oncology
Pediatrics
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