ArticleCancer chemotherapy and pharmacology2021
Population pharmacokinetics and exposure-response of selumetinib and its N-desmethyl metabolite in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Pharmacokinetics and Safety of Selumetinib Granule Formulation in Children With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (SPRINKLE; phase I/II).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.Neuro-oncology · 2024Trial
- Effect of food on capsule and granule formulations of selumetinib.Clinical and translational science · 2022Trial
- A Nonparametric Population Pharmacokinetic Model of Selumetinib in Pediatric Patients Diagnosed With Neurofibromatosis-I or Plexiform Neurofibromas.CPT: pharmacometrics & systems pharmacology · 2026Article
- Selumetinib in Adult Neurofibromatosis 1 with Plexiform Neurofibroma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Physiologically Based Biopharmaceutics Model for Selumetinib Food Effect Investigation and Capsule Dissolution Safe Space - Part I: Adults.Pharmaceutical research · 2023Article
- Population pharmacokinetics of FCN-159, a MEK1/2 inhibitor, in adult patients with advanced melanoma and neurofibromatosis type 1 (NF1) and model informed dosing recommendations for NF1 pediatrics.Frontiers in pharmacology · 2023Article
- Selumetinib-A Comprehensive Review of the New FDA-Approved Drug for Neurofibromatosis.Indian dermatology online journalArticle
- Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas.Neuro-oncology advancesArticle
- Selumetinib in Japanese pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An open-label, phase I study.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeSelumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (≥ 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). We characterized population pharmacokinetics (PK) of selumetinib and its active N-desmethyl metabolite, evaluated exposure-safety/efficacy relationships, and assessed the proposed therapeutic dose of 25 mg/m
methodsPopulation PK modeling and covariate analysis (demographics, formulation, liver enzymes, BSA, patients/healthy volunteers) were based on pooled PK data from adult healthy volunteers (n = 391), adult oncology patients (n = 83) and pediatric patients with NF1-PN (n = 68). Longitudinal selumetinib/metabolite exposures were predicted with the final model. Exposure-safety/efficacy analyses were applied to pediatric patients (dose levels: 20, 25, 30 mg/m
resultsSelumetinib and metabolite concentration-time courses were modeled using a joint compartmental model. Typical selumetinib plasma clearance was 11.6 L/h (95% CI 11.0-12.2 L/ h). Only BSA had a clinically relevant (> 20%) impact on exposure, supporting BSA-based administration in children. Selumetinib and metabolite exposures in responders (≥ 20% PN volume decrease from baseline) and non-responders were largely overlapping, with medians numerically higher in responders. No clear relationships between exposure and safety events were established; exposure was not associated with key adverse events (AEs) including rash acneiform, diarrhea, vomiting, and nausea.
conclusionFindings support continuous selumetinib 25 mg/m
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