Amikacin Pharmacokinetics to Optimize Dosing Recommendations in Neonates With Perinatal Asphyxia Treated With Hypothermia

Summary

As a part of a project on perinatal clinical pharmacology, the primary aim of the present project is to study amikacin pharmacokinetics (PK) and physiology in asphyxiated neonates treated with therapeutic hypothermia and to provide amikacin dosing recommendations, which will be validated prospectively. For this purpose, we aim to first collect retrospective data on amikacin available in neonates treated with hypothermia in the neonatal intensive care unit (NICU)s in Leuven and Amsterdam, and consequently to propose the dosing regimen to be used in the prospective amikacin PK study at our NICU in University Clinical Center (UCC) Sarajevo. At our NICU we aim to collect amikacin PK observations and other covariates in at least 40 neonates while treated with hypothermia and after re-warming period (a paired analysis), and in asphyxiated neonates not treated with hypothermia (control group). We hereby will use a stepwise approach, as initially used to develop and to validate an amikacin dosing regimen in preterm and term neonates (De Cock RFW et al., 2012, Smits A et al, 2015). A 3-step approach will be used, of which different parts will be conducted in different contributing hospitals: 1. Retrospective evaluation of amikacin therapeutic drug monitoring (TDM) in asphyxiated neonates treated with hypothermia (University hospital Leuven, VUmc Amsterdam) 2. Development of population PK model derived amikacin dosing recommendation 3. Prospective PK study with validation of the new dosing regimen (UCC Sarajevo, UCC Tuzla)

Timeline

Start

2018-08-28

Primary completion

2022-08

Completion

2022-12

Publications

• Background De Cock RF, Allegaert K, Schreuder MF, Sherwin CM, de Hoog M, van den Anker JN, Danhof M, Knibbe CA. Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance. Clin Pharmacokinet. 2012 Feb 1;51(2):105-17. doi: 10.2165/11595640-000000000-00000.
• Background Smits A, De Cock RF, Allegaert K, Vanhaesebrouck S, Danhof M, Knibbe CA. Prospective Evaluation of a Model-Based Dosing Regimen for Amikacin in Preterm and Term Neonates in Clinical Practice. Antimicrob Agents Chemother. 2015 Oct;59(10):6344-51. doi: 10.1128/AAC.01157-15. Epub 2015 Jul 27.

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