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

Autor: Paioni P; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland., Jäggi VF; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland., Tilen R; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.; Biopharmacy, Department Pharmaceutical Sciences, University Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland., Seiler M; Pediatric Emergency Department, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland., Baumann P; Department of Intensive Care and Neonatology, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland., Bräm DS; Biopharmacy, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland., Jetzer C; Biopharmacy, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland., Haid RTU; Biopharmacy, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland., Goetschi AN; Biopharmacy, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland., Goers R; Biopharmacy, Department Pharmaceutical Sciences, University Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland., Müller D; Institute of Clinical Chemistry, University Hospital Zurich, Rämistr. 100, CH-8091 Zurich, Switzerland., Coman Schmid D; Scientific IT Services, ETH Zurich, Binzmühlestrasse 130, CH-8092 Zurich, Switzerland.; SIB Swiss Institute of Bioinformatics, Quartier Sorge-Batiment Amphipole, CH-1015 Lausanne, Switzerland., Meyer Zu Schwabedissen HE; Biopharmacy, Department Pharmaceutical Sciences, University Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland., Rinn B; Scientific IT Services, ETH Zurich, Binzmühlestrasse 130, CH-8092 Zurich, Switzerland.; SIB Swiss Institute of Bioinformatics, Quartier Sorge-Batiment Amphipole, CH-1015 Lausanne, Switzerland., Berger C; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland., Krämer SD; Biopharmacy, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2021 Oct 01; Vol. 13 (10). Date of Electronic Publication: 2021 Oct 01.
DOI: 10.3390/pharmaceutics13101596
Abstrakt: 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 SwissPK cdw 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.
Databáze: MEDLINE
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