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Pediatric Drugs
Published in: Pediatric Drugs 3/2018

01-06-2018 | short communication

Optimizing Amikacin Dosage in Pediatrics Based on Population Pharmacokinetic/Pharmacodynamic Modeling

Authors: Saeed Alqahtani, Manal Abouelkheir, Abdullah Alsultan, Yasmine Elsharawy, Aljawharah Alkoraishi, Reem Osman, Wael Mansy

Published in: Pediatric Drugs | Issue 3/2018

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Abstract

Objective

Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens.

Methods

We performed a retrospective chart review in non-critical pediatric patients (aged 1–12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets.

Results

The analysis included 134 amikacin plasma concentrations from 67 patients with a mean ± standard deviation age of 4.1 ± 3.9 years and bodyweight of 15 ± 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 ± 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 ± 7.6 and 2.4 ± 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (Cpeak)/minimum inhibitory concentration (MIC) ≥ 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values.

Conclusion

The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of ≥ 8 mg/l.
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Metadata
Title
Optimizing Amikacin Dosage in Pediatrics Based on Population Pharmacokinetic/Pharmacodynamic Modeling
Authors
Saeed Alqahtani
Manal Abouelkheir
Abdullah Alsultan
Yasmine Elsharawy
Aljawharah Alkoraishi
Reem Osman
Wael Mansy
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 3/2018
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.1007/s40272-018-0288-y

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