ArticleInternational journal of pharmaceutics2012
Enhanced brain accumulation of pazopanib by modulating P-gp and Bcrp1 mediated efflux with canertinib or erlotinib.
Article in International journal of pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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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
31 citing papers in PubMed, 65 citations in OpenAlex.
- Long-term control of grade 3 intracranial solitary fibrous tumor achieved with pazopanib and stereotactic radiotherapy: illustrative case.Journal of neurosurgery. Case lessons · 2026Article
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- Dual inhibitors of P-glycoprotein and breast cancer resistance protein for overcoming the blood-brain barrier: in silico discovery and preclinical evaluation.Archives of pharmacal research · 2025Article
- Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.Cancer biology & medicine · 2025Review
- DNA-PK Inhibition Shows Differential Radiosensitization in Orthotopic GBM PDX Models Based on DDR Pathway Deficits.Molecular cancer therapeutics · 2025Article
- Primary and acquired resistance to first-line therapy for clear cell renal cell carcinoma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Prediction for optimal dosage of pazopanib under various clinical situations using physiologically based pharmacokinetic modeling.Frontiers in pharmacology · 2022Article
- Chemotherapy, targeted therapy and immunotherapy: Which drugs can be safely used in the solid organ transplant recipients?Transplant international : official journal of the European Society for Organ Transplantation · 2021Review
- Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma.The Journal of clinical investigation · 2020Article
- Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration.International journal of molecular sciences · 2020Review
- Coexpression of ABCB1 and ABCG2 in a Cell Line Model Reveals Both Independent and Additive Transporter Function.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- Development of the CNS TAP tool for the selection of precision medicine therapies in neuro-oncology.Journal of neuro-oncology · 2018Article
- Tyrosine kinase inhibitors enhanced the efficacy of conventional chemotherapeutic agent in multidrug resistant cancer cells.Molecular cancer · 2018Review
- Translational gap in ongoing clinical trials for glioma.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2018Review
- Therapeutic Potential and Utility of Elacridar with Respect to P-glycoprotein Inhibition: An Insight from the Published In Vitro, Preclinical and Clinical Studies.European journal of drug metabolism and pharmacokinetics · 2017Review
- Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.Translational research : the journal of laboratory and clinical medicine · 2017Article
- PharmGKB summary: pazopanib pathway, pharmacokinetics.Pharmacogenetics and genomics · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Primary objective of this investigation was to delineate the differential impact of efflux transporters P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) on brain disposition and plasma pharmacokinetics of pazopanib. In addition, this research investigated whether inhibition of these efflux transporters with clinically relevant efflux modulators canertinib or erlotinib could be a viable strategy for improving pazopanib brain delivery. In vitro assays with MDCKII cell monolayers suggested that pazopanib is a high affinity substrate for Bcrp1 and a moderate substrate for P-gp. Co-incubation with specific transport inhibitors restored cell accumulation and completely abolished the directionality of pazopanib flux. Brain and plasma pharmacokinetic studies were conducted in FVB wild type mice in the absence and presence of specific transport inhibitors. Drug levels in plasma and brain were determined using a validated high performance liquid chromatography method using vandetanib as an internal standard. In vivo studies indicated that specific inhibition of either P-gp (by zosuquidar or LY335979) or Bcrp1 (by Ko143) alone did not significantly alter pazopanib brain accumulation. However, dual P-gp/Bcrp1 inhibition by elacridar (GF120918), significantly enhanced pazopanib brain penetration by ~5-fold without altering its plasma concentrations. Thus, even though Bcrp1 showed higher affinity towards pazopanib in vitro, in vivo at the mouse BBB both P-gp and Bcrp1 act in concert to limit brain accumulation of pazopanib. Furthermore, erlotinib and canertinib as clinically relevant efflux modulators efficiently abrogated directionality in pazopanib efflux in vitro and their co-administration resulted in 2-2.5-fold increase in pazopanib brain accumulation in vivo. Further pre-clinical and clinical investigations are warranted as erlotinib or canertinib may have a synergistic pharmacological effect in addition to their primary role of pazopanib efflux modulation as a combination regimen for the treatment of recurrent brain tumors.
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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.