ArticleBritish journal of clinical pharmacology2018
Population pharmacokinetics of the MEK inhibitor selumetinib and its active N-desmethyl metabolite: data from 10 phase I trials.
Article in British journal of clinical pharmacology, 2018. 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.
- A Nonparametric Population Pharmacokinetic Model of Selumetinib in Pediatric Patients Diagnosed With Neurofibromatosis-I or Plexiform Neurofibromas.CPT: pharmacometrics & systems pharmacology · 2026Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Healthy volunteers in first-in-human oncology drug development for small molecules.British journal of clinical pharmacology · 2022Review
- Physiologically Based Pharmacokinetic Modeling for Selumetinib to Evaluate Drug-Drug Interactions and Pediatric Dose Regimens.Journal of clinical pharmacology · 2021Article
- Population pharmacokinetics and exposure-response of selumetinib and its N-desmethyl metabolite in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas.Cancer chemotherapy and pharmacology · 2021Article
- Neurofibromatosis in the Era of Precision Medicine: Development of MEK Inhibitors and Recent Successes with Selumetinib.Current oncology reports · 2021Review
- Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.Clinical pharmacokinetics · 2021Review
- Population pharmacokinetic model with time-varying clearance for lorlatinib using pooled data from patients with non-small cell lung cancer and healthy participants.CPT: pharmacometrics & systems pharmacology · 2021Article
- Reviewing the role of healthy volunteer studies in drug development.Journal of translational medicine · 2018Review
- Population pharmacokinetics of the MEK inhibitor selumetinib and its active N-desmethyl metabolite: data from 10 phase I trials.British journal of clinical pharmacology · 2018Article
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6 authors.
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Abstract
aimsThe aims of the study were to characterize the pharmacokinetics (PK) of selumetinib (AZD6244; ARRY-142886), a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor in clinical development for various indications, and its N-desmethyl metabolite in healthy volunteers, and evaluate clinically important covariates.
methodsA pooled-population PK analysis was performed using a nonlinear mixed-effects approach with plasma concentration data from 346 subjects who received single oral doses of selumetinib 20-75 mg across 10 phase I studies. Absolute bioavailability was determined using intravenous [
resultsA two-compartment linear model with sequential zero-first order absorption and a lag time for the zero-order process was described for selumetinib PK. N-desmethyl metabolite disposition was described by a single compartment with linear elimination, without back transformation. The parent-only and joint models generally described pooled data adequately. For the median subject, not taking interacting drugs, estimates for clearance (CL) and central volume of distribution (V2) for selumetinib in the final joint model were 12.7 l h
conclusionsAnalysis confirmed previous clinical pharmacology study findings of drug-drug interactions and food effects, with additional covariates that influence selumetinib and N-desmethyl selumetinib PK identified. Dose modifications based on these additional covariates were not considered necessary.
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