Clinical Pharmacokinetics

, Volume 57, Issue 10, pp 1217–1228 | Cite as

Clinical Pharmacokinetics of Amikacin in Pediatric Patients: A Comprehensive Review of Population Pharmacokinetic Analyses

  • Sílvia M. Illamola
  • Catherine M. Sherwin
  • J. G. Coen van Hasselt
Review Article


Amikacin plays a key role in the treatment of severe hospital-acquired infections with Gram-negative bacteria. Therapeutic use of amikacin is challenged by high inter-individual variability (IIV) combined with a narrow therapeutic spectrum. Pediatric patients represent a particularly fragile population where adequate dosing is crucial yet challenging to achieve due significant IIV associated with developmental processes and other factors. The current review provides an overview of parametric population pharmacokinetic analyses of amikacin in pediatric patients and associated patient-specific determinants of IIV. We searched PubMed for parametric population pharmacokinetic analyses of amikacin in pediatric patients. Information on patient population, study design, pharmacokinetic model characteristics, and identified patient-specific predictors of IIV was collected. Comparative analyses across studies were conducted to characterize quantitative differences reported for different studies and patient populations. Eight eligible publications were identified, of which six analyses involved neonates up to 3 months of age and two studies investigated older pediatric patients (age 2–17 years). Most commonly included covariates were current body weight for both clearance and volume of distribution, followed by age-related covariates on clearance in neonatal studies (four of six models). Quantitative comparisons of different models reported generally showed similar developmental effects in neonatal populations. The present review provides a comprehensive overview of parametric population pharmacokinetic studies for amikacin. Future studies could address the knowledge gap of patients between 3 months and 2 years of age. Furthermore, systematic studies of additional potential predictors for IIV (e.g., sepsis, inflammatory markers, renal function biomarkers) could be of relevance to address the significant IIV remaining after inclusion of the most commonly identified covariates.


Compliance with Ethical Standards


No sources of funding were used to assist with the preparation of this review.

Conflict of interest

Sílvia M. Illamola, Catherine M. Sherwin, and J. G. Coen van Hasselt have no conflicts of interest that are relevant to the content of this review.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Clinical Pharmacology, Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Pharmacy and Pharmaceutical Technology, School of PharmacyUniversitat de BarcelonaBarcelonaSpain
  3. 3.Biochemistry ServiceHospital Universitari Vall d’Hebron, Universitat Autònoma de BarcelonaBarcelonaSpain
  4. 4.Division of Systems Biomedicine and PharmacologyLeiden Academic Centre for Drug Research, Leiden UniversityLeidenThe Netherlands

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