Evaluation of the pharmacokinetics of glibenclamide tablet given, off label, orally to children suffering from neonatal syndromic hyperglycemia.

Détails

ID Serval
serval:BIB_D7382EF83326
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Evaluation of the pharmacokinetics of glibenclamide tablet given, off label, orally to children suffering from neonatal syndromic hyperglycemia.
Périodique
European journal of clinical pharmacology
Auteur(s)
Bouazza N., Djerada Z., Gozalo C., Busiah K., Beltrand J., Berdugo M., Urien S., Treluyer J.M., Polak M.
ISSN
1432-1041 (Electronic)
ISSN-L
0031-6970
Statut éditorial
Publié
Date de publication
11/2016
Peer-reviewed
Oui
Volume
72
Numéro
11
Pages
1373-1379
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Journal Article
Publication Status: ppublish
Résumé
Glibenclamide (Gb) is used in type II diabetes mellitus but also in the last 10 years, off label, in patients with neonatal syndromic hyperglycemia carrying a mutation of Kir6.2 or SUR1. No studies have reported Gb pharmacokinetics in children. In this study, oral Gb pharmacokinetics was investigated in children in order to describe the concentration time courses, the influence of covariates, and the relationships between drug concentrations and efficacy.
Gb concentrations were measured in 18 children after the switch from subcutaneous insulin to oral tablets of Gb (crushed tablets for 33 % of patients). A total of 229 plasma Gb concentrations and 187 blood glucose measurements were available. A population model was developed with NONMEM.
Body weight was the most significant parameter on clearance and explained a substantial part of the variability. A variant genotype of CYP2C9 (i.e., *1/*2 and *1/*3) explained also a part of the remaining variability on Gb clearance. Patients carrying these allelic variants had a clearance decreased by 45 %. A link between daily area under the curve (AUC <sub>0-24 h</sub> ) and metabolic control diabetes was found.
This study evaluates for the first time the pharmacokinetics of oral Gb in children and constitutes a first step towards dose individualization of this drug in a particularly vulnerable population.
Mots-clé
Administration, Oral, Blood Glucose/analysis, Child, Child, Preschool, Cytochrome P-450 CYP2C9/genetics, Dose-Response Relationship, Drug, Genotype, Glyburide/administration & dosage, Glyburide/blood, Glyburide/pharmacokinetics, Glyburide/therapeutic use, Humans, Hyperglycemia/blood, Hyperglycemia/drug therapy, Hyperglycemia/genetics, Hyperglycemia/metabolism, Hypoglycemic Agents/administration & dosage, Hypoglycemic Agents/blood, Hypoglycemic Agents/pharmacokinetics, Hypoglycemic Agents/therapeutic use, Injections, Subcutaneous, Insulin/administration & dosage, Insulin/therapeutic use, Models, Biological, Mutation, Off-Label Use, Potassium Channels, Inwardly Rectifying/genetics, Sulfonylurea Receptors/genetics, Syndrome, Tablets, Children, Diabetes mellitus, Glibenclamide, Neonatal diabetes mellitus, Neonatal syndromic hyperglycemia, Population pharmacokinetics
Pubmed
Web of science
Création de la notice
28/02/2020 16:05
Dernière modification de la notice
26/03/2020 6:26
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