Evidence map›Paper›PMID 28326681›Full record

Trial reportCPT: pharmacometrics & systems pharmacology2017

Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low-Grade Gliomas.

Y T Patel, V M Daryani, P Patel, D Zhou, J Fangusaro, D J Carlile, P D Martin, L Aarons, C F Stewart

Erratum issuedAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in CPT: pharmacometrics & systems pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Drug metabolism and disposition: the biological fate of chemicals · 2022
    Article
  6. Review
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Y T PatelDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
V M DaryaniDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN; currently at Gilead Sciences, San Francisco, California, USA.
P PatelManchester Pharmacy School, University of Manchester, Manchester, UK.
D ZhouQuantitative Clinical Pharmacology, AstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA.
J FangusaroAnn and Robert H. Lurie Children's Hospital of Chicago and the Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
D J CarlileInnovative Medicine and Early Development, AstraZeneca, Da Vinci Building, Melbourn Science Park, Cambridge, UK, AstraZeneca, UK.
P D MartinQuantitative Clinical Pharmacology, AstraZeneca, Cheshire, UK; currently at Sandoz, Clinical Pharmacology, Holzkirchen, Germany.
L AaronsManchester Pharmacy School, University of Manchester, Manchester, UK.
C F StewartDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Pediatric Brain Tumor Consortium (PBTC)UM1CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Ira J Dunkel, Arzu Onar-Thomas · 2014 to 2026
$41.4M
The Pediatric Brain Tumor Consortium (PBTC)U01CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BOYETT, JAMES MILFORD · 1999 to 2013
$29.2M
NCI NIH HHS P30 CA021765NCI NIH HHS U01 CA081457NCI NIH HHS UM1 CA081457
6 · The paper itself

Abstract

Selumetinib (AZD6244, ARRY-142886), a mitogen activated protein kinases (MEK1 and 2) inhibitor, has been granted orphan drug designation for differentiated thyroid cancer. The primary aim of this analysis was to characterize the population pharmacokinetics of selumetinib and its active metabolite N-desmethyl-selumetinib in patients with cancer. Concentration-time data from adult and pediatric clinical trials were pooled to develop a population pharmacokinetic model using a sequential approach where selumetinib and N-desmethyl-selumetinib data were modeled separately. A sequential zero- and first-order absorption with lag time with a two-compartment model for selumetinib and a two-compartment model for N-desmethyl-selumetinib best described the concentration-time data. Intrapatient variability in absorption was higher than interpatient variability. The apparent drug clearance (CL/F) from the central compartment was 13.5 L/hr (RSE 4.9%). Significant covariates for CL/F were age, alanine aminotransferase, and body surface area. This study confirms that flat dosing is appropriate in adults, whereas body-surface area based dosing should be used in pediatric patients.

Indexed as

Models, BiologicalAdolescentAdultAgedAntineoplastic AgentsBenzimidazolesChildChild, PreschoolCross-Over StudiesDouble-Blind MethodFemaleGliomaHumansMaleMiddle AgedNeoplasmsAntineoplastic AgentsAZD 6244BenzimidazolesProtein Kinase Inhibitors

Identifiers

PMID28326681
PMCPMC5445231

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.