Covariates of amikacin disposition in a large pediatric oncology cohort

I Dewandel, Karel Allegaert, M Renard, A Laenen, A Smits

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: Amikacin pharmacokinetics (PK) in children display large variability due to maturational and disease-related covariates. The objective was to explore amikacin PK in a large pediatric oncology cohort, taking into account within-patient changes. Materials and methods: Clinical data and amikacin therapeutic drug monitoring (TDM) observations were collected retrospectively from children with an oncology diagnosis receiving amikacin during febrile neutropenia. Individual amikacin PK parameters were calculated using a 1-compartment model with instantaneous input and first-order output. This approach was selected based on a pragmatic study design using TDM from routine clinical care, with availability of 2 TDM samples per treatment episode. To explore covariates of clearance (Cl) and volume of distribution (Vd), linear mixed models were used, modelling a random effect for patient to account for clustering due to repeated measurements. Results: Based on 188 amikacin treatment episodes in 114 patients, median (interquartile range) amikacin Cl was 1.37 (1.05; 2.46) L/h and Vd 7.98 (5.66; 12.73) L. Height and creatinemia were significant covariates for Cl (marginal R2 71.1%), while weight, height, and creatinemia determined Vd (marginal R2 59.5%). Conclusion: We described extensive variability of amikacin PK in a large cohort of pediatric oncology patients, including within-patient changes across treatment episodes. Maturational covariates and creatinemia determined amikacin Cl and Vd, while primary non-maturational covariates were not significant. Our observations, based on combined clinical and PK data in children with oncology diagnoses, can be useful to feed dosing software programs to improve drug exposure in special populations.

Original languageEnglish
Pages (from-to)31-41
Number of pages11
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume59
Issue number1
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
The research activities of Anne Smits are supported by the Clinical Research and Education Council of the University Hospitals Leuven.

Funding Information:
The study has not been funded. The re search activities of Anne Smits are supported by the Clinical Research and Education Council of the University Hospitals Leuven.

Publisher Copyright:
© 2021 Dustri-Verlag Dr. K. Feistle

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