Pieter A.J.G. De Cock(1,2,3,4), Sven C. van Dijkman (4), Annick de Jaeger (4), Jef Willems (3), Mieke Carlier (5), Alain G. Verstraete (5,6), Joris R. Delanghe (5,6), Hugo Robays (1), Johan Vande Walle (7), Oscar E. Della Pasqua (4,8,9), Peter De Paepe (2)
(1)Department of Pharmacy, Ghent University Hospital, Ghent, Belgium (2)Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium (3)Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium (4)Leiden Academic Centre for Drug Research, Division of Pharmacology, Leiden, the Netherlands (5)Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium (6)Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium (7)Department of Paediatric Nephrology, Ghent University Hospital, Ghent, Belgium (8)GlaxoSmithKline, Clinical Pharmacology and Simulation, Uxbridge, United Kingdom (9)Department of Clinical Pharmacology and Therapeutics, School of Pharmacy, University College London, London, United Kingdom
Objectives:The objective of this study was to investigate the pharmacokinetics of piperacillin and tazobactam in critically infants and children.
Methods: This pharmacokinetic study enrolled patients admitted to the paediatric intensive care unit in whom intravenous piperacillin-tazobactam was indicated (75 mg/kg q6h). Piperacillin/tazobactam concentrations were measured by a liquid chromatography-tandem mass spectrometry method. Population pharmacokinetic analysis (NONMEM) was conducted.
Results: Piperacillin and tazobactam blood samples were collected from 47 patients (median age: 2.83 years; range: 2 months – 15 years). A two-compartment model for piperacillin and tazobactam best described the data, in which allometric weight scaling and a Hill maturation function were added to scale for size and age. The typical population values of clearance for piperacillin and tazobactam were 4 L/h and 2.52 L/h for a typical child of 14 and 11 kg, respectively. Monte Carlo simulations demonstrated that an intermittent infusion of 75 mg/kg 4 hourly given over 1-2 hours or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24h (based on the piperacillin component) were minimally required to achieve the piperacillin therapeutic target.
Conclusions: Standard intermittent dosing regimens are unlikely to achieve optimal piperacillin-tazobactam exposure in critically ill children with sepsis, thereby risking treatment failure.
Reference: PAGE 25 (2016) Abstr 6006 [www.page-meeting.org/?abstract=6006]
Poster: Drug/Disease modeling - Paediatrics