# Externally validated population pharmacokinetics of amikacin and evaluation of dosage regimen based on achieved serum concentrations in neonates

## TL;DR

This study validates a pharmacokinetic model for amikacin in neonates and finds that intramuscular administration can be as effective as intravenous.

## Contribution

An externally validated population pharmacokinetic model for amikacin in neonates is presented, along with insights on dosing regimens and administration routes.

## Key findings

- 61% of peak and 99% of trough amikacin concentrations were within therapeutic ranges.
- Intramuscular administration resulted in higher peak and trough concentrations compared to intravenous.
- The pharmacokinetic model was shown to be reliable and unbiased through external validation.

## Abstract

Combination antibiotics consisting of beta-lactam and aminoglycoside are commonly utilized in the treatment of neonatal septicaemia. The aims of this study were to (i) develop an externally validated population pharmacokinetic (PK) model, (ii) evaluate the attainment of target peak and trough serum concentrations by the current hospital amikacin dosing protocol and side effects, and (iii) compare intravenous (IV) versus intramuscular (IM) route of amikacin administration, in terms of attaining peak and trough serum concentration targets. Retrospective chart review was carried out over a 5-year period. All neonates who received amikacin with therapeutic drug monitoring performed were included in this study. A one-compartment population PK model was built, and external validation was performed. A total of 181 neonates (534 serum concentrations) were included in the population PK modeling and external validation. There was no apparent systematic bias in the predictions of the model. The external validation performed in the current study found the model to be generally unbiased. Sixty-one percent of the peak and 99% of the trough levels were within the targeted therapeutic ranges of 15–25 and <5 mg/L, respectively. There was no statistical difference in the proportion of trough concentrations that were within therapeutic range for IV as compared to IM, while IM resulted in a higher proportion of trough concentrations within therapeutic range, as well as higher peak concentrations. The current population PK model and external validation study have proven that the PK model built in the current study can be used to conduct reliable population simulations. IM injection can be an alternative route of administration for amikacin in neonates.