ArticleDrug metabolism and drug interactions2014
Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of 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 22 papers.
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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, 42 citations in OpenAlex.
- Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants.Clinical pharmacology in drug development · 2022Trial
- Population Pharmacokinetic and Covariate Analysis of Apatinib, an Oral Tyrosine Kinase Inhibitor, in Healthy Volunteers and Patients with Solid Tumors.Clinical pharmacokinetics · 2017Trial
- Pharmacokinetic modelling of MRI-based liver function for risk assessment in primary sclerosing cholangitis: a prospective pilot study.European radiology experimental · 2026Article
- Evaluating the Utility and Constraints of the Competitive Counter Flow (CCF) Assay in OATP1B1 Substrate Profiling.The AAPS journal · 2026Article
- Transporter-Mediated Cellular Distribution of Tyrosine Kinase Inhibitors as a Potential Resistance Mechanism in Chronic Myeloid Leukemia.Pharmaceutics · 2023Review
- Uptake Transporters at the Blood-Brain Barrier and Their Role in Brain Drug Disposition.Pharmaceutics · 2023Review
- Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy.JCI insight · 2023Article
- Genotyping of the OATP1B1 c. 521 T>C Polymorphism from the Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Specimens: an Optimized Protocol.Bio-protocol · 2019Article
- Decreased Disposition of Anticancer Drugs Predominantly Eliminated via the Liver in Patients with Renal Failure.Current drug metabolism · 2019Review
- Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.Clinical pharmacology and therapeutics · 2018Article
- OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity.The Journal of clinical investigation · 2018Article
- Article
- 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
- 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
- Article
- Novel delivery approaches for cancer therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- Effects of 5-Amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one Intake on Digestive System in a Rat Model of Colon Cancer.TheScientificWorldJournal · 2015Article
- Molecular expression and functional activity of vitamin C specific transport system (SVCT2) in human breast cancer cells.International journal of pharmaceutics · 2014Article
- Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors.Drug metabolism and drug interactions · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe metabolism of tyrosine kinase inhibitors (TKIs) is mainly mediated via hepatic route, but the mechanism responsible for their hepatocellular accumulation is still unknown. This study was designed to understand the contribution of organic anion transporting polypeptides (OATPs) in the hepatic uptake of selected TKIs - pazopanib, canertinib, erlotinib, vandetanib and nilotinib.
methodsMichaelis-Menten (MM) kinetic parameters for TKIs were determined by concentration-dependent cellular accumulation of selected TKIs using Chinese hamster ovary cells - wild type as well as transfected with humanized OATP-1B1 and OATP-1B3 transporter proteins.
resultsThe MM constant (Km) values of OATP-1B1 for nilotinib and vandetanib are 10.14±1.91 and 2.72±0.25 μM, respectively, and Vmax values of OATP-1B1 for nilotinib and vandetanib were 6.95±0.47 and 75.95±1.99 nmol/mg protein per minute, respectively. Likewise, Km values of OATP-1B3 for canertinib, nilotinib and vandetanib were 12.18±3.32, 7.84±1.43 and 4.37±0.79 μM, respectively, and Vmax values of OATP-1B3 for canertinib, nilotinib and vandetanib were 15.34±1.59, 6.75±0.42 and 194.64±10.58 nmol/mg protein per minute, respectively. Canertinib did not exhibit any substrate specificity toward OATP-1B1. Also, erlotinib and pazopanib did not exhibit any substrate specificity toward OATP-1B1 and -1B3.
conclusionsBecause selected TKIs are the substrates of OATP-1B1 and -1B3 expressed in hepatic tissue, these compounds can be regarded as molecular targets for transporter-mediated drug-drug interactions (DDIs). Any alteration in the function of these hepatic OATPs might account for the pharmacokinetic variability of TKIs.
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