ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Phase I-IV Drug Trials on Hepatocellular Carcinoma in Asian Populations: A Systematic Review of Ten Years of Studies.International journal of molecular sciences · 2024Pooled it
- Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide.Clinical and translational science · 2017Trial
- Population Pharmacokinetic and Covariate Analysis of Apatinib, an Oral Tyrosine Kinase Inhibitor, in Healthy Volunteers and Patients with Solid Tumors.Clinical pharmacokinetics · 2017Trial
- In Vivo Evidence of Human Organic Anion Transporting Polypeptide (OATP) 1B1 and OATP1B3 Mediated Disposition of Glycyrrhizin and Its Drug-Drug Interactions in Humanized Mice.Phytotherapy research : PTR · 2026Article
- Quantification of Binding of Small Molecules to Native Kinases by Flow Cytometry Reveals Divergence from Biochemical Affinities.Journal of the American Chemical Society · 2026Article
- Innovative strategies to overcome cancer drug resistance: from nanodelivery systems to targeted therapeutics.Discover oncology · 2026Review
- Evaluating the Utility and Constraints of the Competitive Counter Flow (CCF) Assay in OATP1B1 Substrate Profiling.The AAPS journal · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Harnessing the microbiome: unveiling the influence of the gut microbiota on hepatobiliary cancer therapeutic strategies.Clinical and molecular hepatology · 2026Review
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Association Study of OATP1B3 Polymorphisms on Hepatic Uptake and Drug-Drug InteractionACS omega · 2025Article
- Profiling Interactions Between Bicyclol and SLC/ABC Transporters: Advancing Clinical Safety and Efficacy in Combination Therapy.Pharmaceutical research · 2025Article
- Beyond the obvious: targeting the SLC transportome and non-canonical drug transport mechanisms in cancer therapy.Investigational new drugs · 2025Review
- Decitabine regulates the resistance of HCC to sorafenib through demethylation.Clinical epigenetics · 2025Article
- Comparative Neurotoxic Effects of Doxorubicin and Sunitinib: An In Vitro Study on Human Dopaminergic Neuronal Cells.Molecules (Basel, Switzerland) · 2025Article
- OATP1B-type Transport Function Is a Determinant of Aromatase Inhibitor-Associated Arthralgia Susceptibility.Cancer research communications · 2025Article
- Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.Acta pharmaceutica Sinica. B · 2024Article
- Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen.Cancer research communications · 2024Article
- Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model.Molecular pharmaceutics · 2024Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeMany tyrosine kinase inhibitors (TKI) undergo extensive hepatic metabolism, but mechanisms of their hepatocellular uptake remain poorly understood. We hypothesized that liver uptake of TKIs is mediated by the solute carriers OATP1B1 and OATP1B3. EXPERIMENTAL
designTransport of crizotinib, dasatinib, gefitinib, imatinib, nilotinib, pazopanib, sorafenib, sunitinib, vandetanib, and vemurafenib was studied in vitro using artificial membranes (PAMPA) and HEK293 cell lines stably transfected with OATP1B1, OATP1B3, or the ortholog mouse transporter, Oatp1b2. Pharmacokinetic studies were conducted with Oatp1b2-knockout mice and humanized OATP1B1- or OATP1B3-transgenic mice.
resultsAll 10 TKIs were identified as substrates of OATP1B1, OATP1B3, or both. Transport of sorafenib was investigated further, as its diffusion was particularly low in the PAMPA assay (<4%) than other TKIs that were transported by both OATP1B1 and OATP1B3. Whereas Oatp1b2 deficiency in vivo had minimal influence on parent and active metabolite N-oxide drug exposure, plasma levels of the glucuronic acid metabolite of sorafenib (sorafenib-glucuronide) were increased more than 8-fold in Oatp1b2-knockout mice. This finding was unrelated to possible changes in intrinsic metabolic capacity for sorafenib-glucuronide formation in hepatic or intestinal microsomes ex vivo. Ensuing experiments revealed that sorafenib-glucuronide was itself a transported substrate of Oatp1b2 (17.5-fold vs. control), OATP1B1 (10.6-fold), and OATP1B3 (6.4-fold), and introduction of the human transporters in Oatp1b2-knockout mice provided partial restoration of function.
conclusionsThese findings signify a unique role for OATP1B1 and OATP1B3 in the elimination of sorafenib-glucuronide and suggest a role for these transporters in the in vivo handling of glucuronic acid conjugates of drugs.
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