O-107 Prospective Validation Of A Model-based Dosing Regimen For Amikacin In Preterm And Term Neonates

Abstract

<h3>Background and aims</h3> An essential step in drug dosing optimalisation is prospective validation of newly proposed dosing regimens. Based on a recently published population pharmacokinetic (PK) model, a neonatal amikacin dosing regimen was developed. The aim of the current study was to prospectively validate this model-derived dosing regimen. <h3>Methods</h3> Routine amikacin therapeutic drug monitoring (TDM) concentrations were prospectively collected. To test efficacy of the dosing regimen, early observed TDM results (i.e. prior to and 1 h after the second intravenous amikacin dose) reaching target concentrations (trough &lt;3 mg/L, peak &gt;24 mg/L) were defined. To test stability and accuracy of the model, all observed concentrations were compared with the predicted concentrations and a normalised prediction distribution error (NPDE) was performed. Monte Carlo simulations were used to evaluate amikacin exposure. <h3>Results</h3> In total, 1195 TDM results of 579 neonates [median gestational age 34 (range 24–41) weeks, postnatal age 2 (range 1–30) days] were included. Sixty percent of the early trough levels was below 3 mg/L, 90.4% of the peak levels reached 24 mg/L. Comparable parameter estimates were obtained between the final PK model and the prospective dataset. No trend was seen in the NPDE <i>versus</i> time and the NPDE <i>versus</i> predicted concentrations. Based on the Monte Carlo simulations, peak concentrations above 24 mg/L were reached in almost all patient subgroups. <h3>Conclusions</h3> After 14 years experience of amikacin dosing optimalisation in (pre)term neonates, a model-based dosing algorithm was prospectively validated confirming its efficacy, stability and accuracy over the entire neonatal population.