ArticleDrug metabolism and drug interactions2014
Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors.
Article in Drug metabolism and drug interactions, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 40 citations in OpenAlex.
- Population Pharmacokinetic and Covariate Analysis of Apatinib, an Oral Tyrosine Kinase Inhibitor, in Healthy Volunteers and Patients with Solid Tumors.Clinical pharmacokinetics · 2017Trial
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.Drug design, development and therapy · 2025Review
- Influence of Tyrosine Kinase Inhibition on Organic Anion Transporting Polypeptide 1B3-Mediated Uptake.Molecular pharmacology · 2022Article
- Regulation of OATP1B1 Function by Tyrosine Kinase-mediated Phosphorylation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors.Pharmaceutics · 2020Review
- Interaction between phytotherapy and oral anticancer agents: prospective study and literature review.Medical oncology (Northwood, London, England) · 2019Review
- OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity.The Journal of clinical investigation · 2018Article
- Investigation of the Importance of Multidrug Resistance-Associated Protein 4 (Mrp4/Abcc4) in the Active Efflux of Anionic Drugs Across the Blood-Brain Barrier.Journal of pharmaceutical sciences · 2017Article
- PharmGKB summary: pazopanib pathway, pharmacokinetics.Pharmacogenetics and genomics · 2017Review
- Harnessing Solute Carrier Transporters for Precision Oncology.Molecules (Basel, Switzerland) · 2017Review
- Unmasking the Role of Uptake Transporters for Digoxin Uptake Across the Barriers of the Central Nervous System in Rat.Journal of central nervous system disease · 2017Article
- Pharmacokinetic Interaction of Rifampicin with Oral Versus Intravenous Anticancer Drugs: Challenges, Dilemmas and Paradoxical Effects Due to Multiple Mechanisms.Drugs in R&D · 2016Review
- Molecular expression and functional activity of vitamin C specific transport system (SVCT2) in human breast cancer cells.International journal of pharmaceutics · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe potential of tyrosine kinase inhibitors (TKIs) interacting with other therapeutics through hepatic uptake transporter inhibition has not been fully delineated in drug-drug interactions (DDIs). This study was designed to estimate the half-maximal inhibitory concentration (IC50) values of five small-molecule TKIs (pazopanib, nilotinib, vandetanib, canertinib and erlotinib) interacting with organic anion-transporting polypeptides (OATPs): OATP-1B1 and -1B3.
methodsThe IC50 values of TKIs and rifampicin (positive control) were determined by concentration-dependent inhibition of TKIs on cellular accumulation of radiolabeled probe substrates [3H]estrone sulfate and [3H]cholecystokinin octapeptide. Chinese hamster ovary cells transfected with humanized OATP-1B1 and OATP-1B3 transporter proteins, respectively, were utilized to carry out these studies.
resultsPazopanib and nilotinib show inhibitory activity on OATP-1B1 transporter protein. IC50 values for rifampicin, pazopanib and nilotinib were 10.46±1.15, 3.89±1.21 and 2.78±1.13 μM, respectively, for OATP-1B1 transporter. Vandetanib, canertinib and erlotinib did not exhibit any inhibitory potency toward OATP-1B1 transporter protein. Only vandetanib expressed inhibitory potential toward OATP-1B3 transporter protein out of the five selected TKIs. IC50 values for rifampicin and vandetanib for OATP-1B3 transporter inhibition were 3.67±1.20 and 18.13±1.21 μM, respectively. No significant inhibition in the presence of increasing concentrations of pazopanib, nilotinib, canertinib and erlotinib were observed for OATP-1B3 transporter.
conclusionsBecause selected TKIs are inhibitors of OATP-1B1 and -1B3 expressed in hepatic tissue, these compounds can be regarded as molecular targets for transporter-mediated DDIs. These findings provide the basis for further preclinical and clinical studies investigating the transporter-based DDI potential of TKIs.
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