ArticlePharmaceutical research2008
Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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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Who cites it
19 citing papers in PubMed, 69 citations in OpenAlex.
- Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs.International journal of molecular sciences · 2025Article
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- Development of 3D-Bioprinted Colitis-Mimicking Model to Assess Epithelial Barrier Function Using Albumin Nano-Encapsulated Anti-Inflammatory Drugs.Biomimetics (Basel, Switzerland) · 2023Article
- In Vitro Evaluation of the Interaction of Seven Biologically Active Components inMolecules (Basel, Switzerland) · 2022Article
- The pharmaceutical excipient PEG400 affect the absorption of baicalein in Caco-2 monolayer model by interacting with UDP-glucuronosyltransferases and efflux transport proteins.Pharmacology research & perspectives · 2022Article
- Claudin-5 binder enhances focused ultrasound-mediated opening in anTheranostics · 2022Article
- Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions.iScience · 2018Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Review
- Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?American journal of cancer research · 2017Review
- Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.Molecules (Basel, Switzerland) · 2016Article
- Membrane Assays to Characterize Interaction of Drugs with ABCB1.The Journal of membrane biology · 2015Article
- FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models.American journal of translational research · 2015Article
- Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance.Biochemical pharmacology · 2012Review
- Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression.Chinese journal of cancer · 2012Review
- Human ABCG2: structure, function, and its role in multidrug resistance.International journal of biochemistry and molecular biology · 2012Article
- Multidrug resistance in breast cancer: from in vitro models to clinical studies.International journal of breast cancer · 2011Article
- Factors affecting the in vivo lactone stability and systemic clearance of the lipophilic camptothecin analogue AR-67.Pharmaceutical research · 2010Article
- Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid.Cancer research · 2009Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the underlying mechanism of low bioavailabilities of the water-soluble camptothecin derivatives, belotecan and topotecan.
methodsThe bioavailability of belotecan and topotecan in rats was determined following oral administration of each drug at a dose of 5 mg/kg body weight. The vectorial transport of each drug was measured in Caco-2 and engineered MDCK II cells.
resultsThe bioavailability of belotecan (11.4%) and topotecan (32.0%) in rats was increased to 61.5% and 40.8%, respectively, by the preadministration of CsA at a dose of 40 mg/kg. Contrary to the absorptive transport, the secretory transport of these drugs across the Caco-2 cell monolayer was concentration-dependent, saturable, and significantly inhibited by the cis presence of verapamil (a P-gp substrate), MK-571 (an MRP inhibitor), bromosulfophthalein (BSP, an MRP2 inhibitor), fumitremorgin C (FTC, a BCRP inhibitor) and cyclosporine A (CsA, an inhibitor of P-gp and BCRP, and a substrate of P-gp) suggesting the involvement of these transporters, which could be further confirmed in MDCKII/P-gp, MDCKII/MRP2 and MDCKII/BCRP cells.
conclusionThe involvement of secretory transporters P-gp, MRP2 and BCRP, particularly for belotecan, as well as a low passive permeability, appears to be responsible for the low bioavailability of belotecan and topotecan.
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