Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis.
ABCB1
P-glycoprotein
Pediatric drug development
Population pharmacokinetic analysis
Vinorelbine
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
31
01
2022
accepted:
04
06
2022
pubmed:
26
6
2022
medline:
23
7
2022
entrez:
25
6
2022
Statut:
ppublish
Résumé
Better understanding of pharmacokinetics of oral vinorelbine (VNR) in children would help predicting drug exposure and, beyond, clinical outcome. Here, we have characterized the population pharmacokinetics of oral VNR and studied the factors likely to explain the variability observed in VNR exposure among young patients. We collected blood samples from 36 patients (mean age 11.6 years) of the OVIMA multicentric phase II study in children with recurrent/progressive low-grade glioma. Patients received 60 mg/m A three-compartment model, with a delayed double zero-order absorption and a first-order elimination, best described VNR pharmacokinetics in children. Typical population estimates for the apparent central volume of distribution (V Beyond canonical BSA and leukocytes, ABCB1-rs2032582 polymorphism showed a meaningful impact on VNR systemic exposure. Simulations showed that the identified covariates could have an impact on both efficacy and toxicity outcomes. Thus, a personalized dosing strategy, using those covariates, could help to optimize the efficacy/toxicity balance of VNR in children.
Identifiants
pubmed: 35751658
doi: 10.1007/s00280-022-04446-y
pii: 10.1007/s00280-022-04446-y
doi:
Substances chimiques
Vinorelbine
Q6C979R91Y
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
29-44Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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