A Pharmacokinetics, Efficacy, and Safety Study of Gadoterate Meglumine in Pediatric Subjects Aged Younger Than 2 Years.

Détails

ID Serval
serval:BIB_59DC1D123346
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A Pharmacokinetics, Efficacy, and Safety Study of Gadoterate Meglumine in Pediatric Subjects Aged Younger Than 2 Years.
Périodique
Investigative radiology
Auteur(s)
Scala M., Koob M., de Buttet S., Bourrinet P., Felices M., Jurkiewicz E.
ISSN
1536-0210 (Electronic)
ISSN-L
0020-9996
Statut éditorial
Publié
Date de publication
02/2018
Peer-reviewed
Oui
Volume
53
Numéro
2
Pages
70-79
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The primary objective of this study was to investigate the pharmacokinetic profile of gadoterate meglumine in pediatric patients younger than 2 years; the secondary objectives were to document its efficacy and safety.
This was a Phase IV open-label, prospective study conducted in 9 centers (4 countries). Forty-five patients younger than 2 years with normal estimated glomerular filtration rate and scheduled to undergo routine gadolinium-enhanced magnetic resonance imaging (MRI) of any organ were included and received a single intravenous injection of gadoterate meglumine (0.1 mmol/kg). To perform the population pharmacokinetics analysis, 3 blood samples per subject were drawn during 3 time windows at time points allocated by randomization.
Gadoterate meglumine concentrations were best fitted using a 2-compartmental model with linear elimination from central compartment. The median total clearance adjusted to body weight was estimated at 0.06 L/h per kg and increased with estimated glomerular filtration rate according to a power model. The median volume of distribution at steady state (Vss) adjusted to body weight was estimated at 0.047 L/kg. Estimated median terminal half-life (t1/2β) was 1.35 h, and the median systemic exposure (area under the curve) was 1591 μmol h/L. Efficacy was assessed by comparing precontrast +postcontrast images to precontrast images in a subset of 28 subjects who underwent an MRI examination of brain, spine, and associated tissues. A total of 28 lesions were identified and analyzed in 15 subjects with precontrast images versus 30 lesions in 16 subjects with precontrast + postcontrast images. Lesion visualization was improved with a mean (SD) increase in scores at subject level of 0.7 (1.0) for lesion border delineation, 0.9 (1.6) for internal morphology, and 3.1 (3.2) for contrast enhancement. Twenty-six adverse events occurred postinjection in 13 subjects (28.9%), including 3 serious reported in 1 subject (2.2%). One subject (2.2%) experienced 1 rash of moderate intensity considered as related to gadoterate meglumine.
The pharmacokinetic profile of gadoterate meglumine after a single intravenous injection of 0.1 mmol/kg was appropriately described in newborns and infants younger than 2 years, for whom no dose adjustment is required. The improved efficacy of gadoterate meglumine for contrast-enhanced MRI examination of brain, spine, and associated tissues, as well as its good safety profile, was also demonstrated in this population.

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Création de la notice
13/11/2017 15:29
Dernière modification de la notice
20/08/2019 14:13
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