Gentamicin Population Pharmacokinetics in Pediatric Patients—A Prospective Study with Data Analysis Using the saemix Package in R

The aminoglycoside gentamicin is used for the empirical treatment of pediatric infections. It has a narrow therapeutic window. In this prospective study at University Children’s Hospital Zurich, Switzerland, we aimed to characterize the pharmacokinetics of gentamicin in pediatric patients and predic...

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Published in:Pharmaceutics Vol. 13; no. 10; p. 1596
Main Authors: Paioni, Paolo, Jäggi, Vera F., Tilen, Romy, Seiler, Michelle, Baumann, Philipp, Bräm, Dominic S., Jetzer, Carole, Haid, Robin T. U., Goetschi, Aljoscha N., Goers, Roland, Müller, Daniel, Coman Schmid, Diana, Meyer zu Schwabedissen, Henriette E., Rinn, Bernd, Berger, Christoph, Krämer, Stefanie D.
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01.10.2021
MDPI
Subjects:
Antibiotics
Bacteria
Data analysis
Data warehouses
dosing regimen
Drug dosages
Drug resistance
E coli
gentamicin
non-linear mixed-effects modeling
Open source software
open-source
Pathogens
Patients
Pediatrics
Pharmacokinetics
Plasma
population pharmacokinetics
Public domain
saemix
Sepsis
United States > US
Switzerland
non-linear mixed-effects modeling
saemix
gentamicin
open-source
dosing regimen
R-project
population pharmacokinetics
ISSN:1999-4923, 1999-4923
Online Access:Get full text
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Summary:The aminoglycoside gentamicin is used for the empirical treatment of pediatric infections. It has a narrow therapeutic window. In this prospective study at University Children’s Hospital Zurich, Switzerland, we aimed to characterize the pharmacokinetics of gentamicin in pediatric patients and predict plasma concentrations at typical recommended doses. We recruited 109 patients aged from 1 day to 14 years, receiving gentamicin (7.5 mg/kg at age ≥ 7 d or 5 mg/kg). Plasma levels were determined 30 min, 4 h and 24 h after the infusion was stopped and then transferred, together with patient data, to the secure BioMedIT node Leonhard Med. Population pharmacokinetic modeling was performed with the open-source R package saemix on the SwissPKcdw platform in Leonhard Med. Data followed a two-compartment model. Bodyweight, plasma creatinine and urea were identified as covariates for clearance, with bodyweight as a covariate for central and peripheral volumes of distribution. Simulations with 7.5 mg/kg revealed a 95% CI of 13.0–21.2 mg/L plasma concentration at 30 min after the stopping of a 30-min infusion. At 24 h, 95% of simulated plasma levels were <1.8 mg/L. Our study revealed that the recommended dosing is appropriate. It showed that population pharmacokinetic modeling using R provides high flexibility in a secure environment.
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These authors contribute equally to this paper.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13101596