ArticleThe Journal of pharmacology and experimental therapeutics2012
Brain distribution of cediranib is limited by active efflux at the blood-brain barrier.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Receptor tyrosine kinase targeted therapies in glioblastoma: a systematic review.Frontiers in medicine · 2026Pooled it
- Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme.Journal of neuro-oncology · 2013Trial
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- P-glycoprotein Mediates Resistance to the Anaplastic Lymphoma Kinase Inhiitor Ensartinib in Cancer Cells.Cancers · 2022Article
- Acyclovir Brain Disposition: Interactions with P-gp, Bcrp, Mrp2, and Oat3 at the Blood-Brain Barrier.European journal of drug metabolism and pharmacokinetics · 2022Article
- Overexpression of ABCB1 and ABCG2 contributes to reduced efficacy of the PI3K/mTOR inhibitor samotolisib (LY3023414) in cancer cell lines.Biochemical pharmacology · 2020Article
- Theoretical Prediction of the Complex P-Glycoprotein Substrate Efflux Based on the Novel Hierarchical Support Vector Regression Scheme.Molecules (Basel, Switzerland) · 2018Article
- Revisiting the role of ABC transporters in multidrug-resistant cancer.Nature reviews. Cancer · 2018Review
- Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas.Molecular cancer therapeutics · 2017Article
- Review
- Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders.Brain research · 2015Review
- Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model.The Journal of pharmacology and experimental therapeutics · 2015Article
- Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1).Pharmaceutical research · 2015Article
- Drug access to the central nervous system in Alzheimer's disease: preclinical and clinical insights.Pharmaceutical research · 2015Review
- Molecularly targeted therapies for recurrent glioblastoma: current and future targets.Neurosurgical focus · 2014Review
- ABC transporters in multi-drug resistance and ADME-Tox of small molecule tyrosine kinase inhibitors.Pharmaceutical research · 2014Review
- Factors influencing the CNS distribution of a novel MEK-1/2 inhibitor: implications for combination therapy for melanoma brain metastases.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Bayesian approach to estimate AUC, partition coefficient and drug targeting index for studies with serial sacrifice design.Pharmaceutical research · 2014Article
- Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors.Drug metabolism and drug interactions · 2014Article
- Pharmacokinetic assessment of efflux transport in sunitinib distribution to the brain.The Journal of pharmacology and experimental therapeutics · 2013Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Cediranib is an orally active tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor family. Because of its potent antiangiogenic and antitumor activities, cediranib has been evaluated for therapy in glioma, a primary brain tumor. This study investigated the influence of two important efflux transporters at the blood-brain barrier, P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), on the delivery of cediranib to the central nervous system. In vitro studies indicated that cediranib is a dual substrate for both P-gp and Bcrp. It is noteworthy that in spite of the in vitro data the in vivo mouse disposition studies conclusively showed that P-gp was the dominant transporter restricting the brain distribution of cediranib. The brain-to-plasma partitioning (AUC(brain)/AUC(plasma), where AUC is area under the curve) and the steady-state brain-to-plasma concentration ratio of cediranib were approximately 20-fold higher in Mdr1a/b⁻/⁻ and Mdr1a/b⁻/⁻Bcrp1⁻/⁻ mice compared with wild-type and Bcrp1⁻/⁻ mice. Moreover, there was no significant difference in brain distribution of cediranib between wild-type and Bcrp1⁻/⁻ mice and between Mdr1a/b⁻/⁻ and Mdr1a/b⁻/⁻Bcrp1⁻/⁻ mice. These results show that, unlike other tyrosine kinase inhibitors that are dual substrates for P-gp and Bcrp, Bcrp does not restrict the distribution of cediranib across the blood-brain barrier. We also show that inhibition of P-gp using specific or nonspecific inhibitors resulted in significantly enhanced delivery of cediranib to the brain. Concurrent administration of cediranib with chemical modulators of efflux transporters can be used as a strategy to enhance delivery and thus efficacy of cediranib in the brain. These findings are clinically relevant to the efficacy of cediranib chemotherapy in glioma.
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Registered trials
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.