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Pediatric Drugs

, Volume 20, Issue 3, pp 265–272 | Cite as

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

  • Saeed Alqahtani
  • Manal Abouelkheir
  • Abdullah Alsultan
  • Yasmine Elsharawy
  • Aljawharah Alkoraishi
  • Reem Osman
  • Wael Mansy
short communication

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.

Notes

Compliance with Ethical Standards

Funding

The authors acknowledge financial support from the College of Pharmacy Research Center and the Deanship of Scientific Research, King Saud University (Riyadh, Saudi Arabia).

Conflict of interest

Saeed Alqahtani, Manal Abouelkheir, Abdullah Alsultan, Yasmine Elsharawy, Aljawharah Alkoraishi, Reem Osman, and Wael Mansy have no conflicts of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Clinical Pharmacokinetics and Pharmacodynamics UnitKing Saud University Medical CityRiyadhSaudi Arabia
  3. 3.Pediatric Clinical Pharmacy Services, King Saud University Medical CityKing Saud UniversityRiyadhSaudi Arabia
  4. 4.Drug and Poison Information Center, King Saud University Medical CityKing Saud UniversityRiyadhSaudi Arabia
  5. 5.Drug Information Center, Sultan Bin Abdulaziz Humanitarian CityKing Saud UniversityRiyadhSaudi Arabia

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