Evidence map›Paper›PMID 24113148›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2013

Pharmacokinetic assessment of efflux transport in sunitinib distribution to the brain.

Rajneet K Oberoi, Rajendar K Mittapalli, William F Elmquist

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% of its field
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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Sunitinib attenuates secondary injury via the regulation of peri-hematomal microglia at the acute phase of intracerebral hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
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  8. Article
  9. Review
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  14. Blood-Brain Barrier in Brain Tumors: Biology and Clinical Relevance.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Rajneet K OberoiDepartment of Pharmaceutics, Brain Barriers Research Center, University of Minnesota, Minneapolis, Minnesota.
Rajendar K Mittapalli
William F Elmquist
University of Minnesota · USPharmac · NZ

Funding

Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
Influence of Anti-Angiogenic Therapy on Drug Delivery to Brain TumorsR01NS077921 · NINDS · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, SARKARIA, JANN N. · 2012 to 2016
$2.5M
Improving Delivery of Molecularly-Targeted Therapy to Invasive Glioma CellsR01CA138437 · NCI · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, OHLFEST, JOHN R · 2010 to 2014
$1.5M
NCI NIH HHS CA138437NCI NIH HHS P50 CA108961NCI NIH HHS R01 CA138437NINDS NIH HHS NS077921NINDS NIH HHS R01 NS077921
6 · The paper itself

Abstract

This study quantitatively assessed transport mechanisms that limit the brain distribution of sunitinib and investigated adjuvant strategies to improve its brain delivery for the treatment of glioblastoma multiforme (GBM). Sunitinib has not shown significant activity in GBM clinical trials, despite positive results seen in preclinical xenograft studies. We performed in vivo studies in transgenic Friend leukemia virus strain B mice: wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) genotypes were examined. The brain-to-plasma area under the curve ratio after an oral dose (20 mg/kg) was similar to the steady-state tissue distribution coefficient, indicating linear distribution kinetics in mice over this concentration range. Furthermore, the distribution of sunitinib to the brain increased after administration of selective P-glycoprotein (P-gp) or breast cancer resistance protein (Bcrp) pharmacological inhibitors and a dual inhibitor, elacridar, comparable to that of the corresponding transgenic genotype. The brain-to-plasma ratio after coadministration of elacridar in wild-type mice was ≈ 12 compared with ≈ 17.3 in Mdr1a/b(-/-)Bcrp1(-/-) mice. Overall, these findings indicate that there is a cooperation at the blood-brain barrier (BBB) in restricting the brain penetration of sunitinib, and brain delivery can be enhanced by administration of a dual inhibitor. These data indicate that the presence of cooperative efflux transporters, P-gp and Bcrp, in an intact BBB can protect invasive glioma cells from chemotherapy. Thus, one may consider the use of transporter inhibition as a powerful adjuvant in the design of future clinical trials for the targeted delivery of sunitinib in GBM.

Indexed as

AnimalsAntineoplastic AgentsArea Under CurveATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Blood-Brain BarrierBrainChromatography, High Pressure LiquidData Interpretation, StatisticalHalf-LifeIndolesMiceMice, KnockoutPyrrolesAbcg2 protein, mouseAntineoplastic AgentsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Indolesmultidrug resistance protein 3PyrrolesSunitinib

Identifiers

PMID24113148
PMCPMC3836310
OpenAlexW2110475445

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.