Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low-grade glioma.

between-subject variability exposure matching low-grade glioma non-compartmental analysis paediatrics pharmacokinetics vinorelbine

Journal

British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323

Informations de publication

Date de publication:
05 2022
Historique:
revised: 29 09 2021
received: 21 06 2021
accepted: 21 10 2021
pubmed: 29 10 2021
medline: 13 4 2022
entrez: 28 10 2021
Statut: ppublish

Résumé

There is a crucial need for pharmacokinetic (PK) data on oral vinorelbine (VNR) in the paediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). A multicentre, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumours, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. PK analysis included 36 patients with a median age (range) of 11 (6-17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration-response relationships of VNR among paediatric patients.

Identifiants

pubmed: 34709655
doi: 10.1111/bcp.15131
doi:

Substances chimiques

Vinorelbine Q6C979R91Y

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2096-2117

Informations de copyright

© 2021 British Pharmacological Society.

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Auteurs

Mourad Hamimed (M)

SMARTc Unit, Cancer Research Center of Marseille, Inserm U1068 - CNRS UMR 7258 - Aix-Marseille University U105, Marseille, France.
Inria - Inserm COMPO team, Centre Inria Sophia Antipolis - Méditerranée, Inserm U1068 - CNRS UMR 7258 - Aix-Marseille University U105, Marseille, France.

Florence Gattacceca (F)

SMARTc Unit, Cancer Research Center of Marseille, Inserm U1068 - CNRS UMR 7258 - Aix-Marseille University U105, Marseille, France.
Inria - Inserm COMPO team, Centre Inria Sophia Antipolis - Méditerranée, Inserm U1068 - CNRS UMR 7258 - Aix-Marseille University U105, Marseille, France.

Nicolas André (N)

SMARTc Unit, Cancer Research Center of Marseille, Inserm U1068 - CNRS UMR 7258 - Aix-Marseille University U105, Marseille, France.
Department of Pediatric Oncology, La Timone University Hospital of Marseille, APHM, Marseille, France.

Emmanuelle Tresch-Bruneel (E)

Department of Biostatistics, Oscar Lambret Cancer Center, Lille, France.

Alicia Probst (A)

Département de la Recherche Clinique et Innovation, Oscar Lambret Cancer Center, Lille, France.

Pascal Chastagner (P)

Service d'hémato-oncologie pédiatrique, Nancy University Hospital, Nancy, France.

Anne Pagnier (A)

Service d'hémato-oncologie pédiatrique, Grenoble University Hospital, Grenoble, France.

Emilie De Carli (E)

Service d'hémato-oncologie pédiatrique, Angers University Hospital, Angers, France.

Natacha Entz-Werlé (N)

Pédiatrie Onco-Hématologie Université de Strasbourg, CHRU Hautepierre, - UMR CNRS 7021, Strasbourg, France.

Jacques Grill (J)

Département de Cancérologie de l'Enfant et de l'Adolescent et UMR CNRS 8203, Université Paris Saclay, Gustave Roussy, Villejuif, France.

Isabelle Aerts (I)

SIREDO Centre (Care, innovation and research in paediatric, adolescent and young adult oncology), Institut Curie-Oncology Center, Paris, France.

Didier Frappaz (D)

Institute of Pediatric Hematology and Oncology IHOPe, Léon Bérard Cancer Center, Lyon, France.

Anne-Isabelle Bertozzi-Salamon (AI)

Service d'hémato-oncologie pédiatrique, Toulouse University Hospital, Toulouse, France.

Caroline Solas (C)

Unité des Virus Émergents (UVE), Aix-Marseille Univ-IRD 190-Inserm 1207, Marseille, France.
Clinical Pharmacokinetics and Toxicology Laboratory, La Timone University Hospital of Marseille, APHM, Marseille, France.

Pierre Leblond (P)

Institute of Pediatric Hematology and Oncology IHOPe, Léon Bérard Cancer Center, Lyon, France.
Department of Pediatric Oncology, Oscar Lambret Cancer Center, Lille, France.

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