A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1‐Related Plexiform Neurofibromas and Healthy Volunteers
Rattachement africain : kr, us, ch. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low‐ and high‐fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N‐desmethyl selumetinib. The dataset comprised 511 subjects from 15 clinical trials who received ≥1 dose of selumetinib and provided ≥1 measurable postdose concentration of selumetinib and N‐desmethyl selumetinib. A 2‐compartment model with sequential 0‐ and 1st‐order delayed absorption and 1st‐order elimination adequately described selumetinib PK characteristics. A 1‐compartment model reasonably described N‐desmethyl selumetinib PK characteristics over time simultaneously with selumetinib. Selumetinib geometric mean area under the concentration–time curve ratio (1‐sided 90% confidence interval [CI] lower bound) was 76.9% (73.3%) with a low‐fat meal and 79.3% (76.3%) with a high‐fat meal versus fasting. The lower bound of the 1‐sided 90% CI demonstrated a difference of <30% between fed and fasted states. Considering the flat exposure‐response relationship within the dose range (20‐30 mg/m2), the observed range of exposure, and the variability in the SPRINT trial, this was not considered clinically relevant.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1‐Related Plexiform Neurofibromas and Healthy Volunteers
- Date Crossref
- 09/04/2024
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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AstraZeneca (South Korea) pays non établi dans la noticeEntreprise
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AstraZeneca (United States) pays non établi dans la noticeEntreprise
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Alexion Pharma (Switzerland) pays non établi dans la noticeEntreprise
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Inc. Merck & Co. pays non établi dans la noticeEntreprise
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Clinical Pharmacology and Safety Sciences Alexion pays non établi dans la noticeÉtablissement de santé
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These authors contributed equally to this work as co-first authors pays non établi dans la noticeInstitution
AstraZeneca (South Korea), AstraZeneca (United States) et Alexion Pharma (Switzerland), avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.