ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Sorafenib hepatobiliary disposition: mechanisms of hepatic uptake and disposition of generated metabolites.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide.Clinical and translational science · 2017Trial
- 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
- Teaching an Old Drug a New Trick: Targeting Treatment Resistance in Genitourinary Cancers.Journal of cellular signaling · 2024Article
- Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1).Journal of hepatocellular carcinoma · 2024Article
- Development and validation of a UPLC-MS/MS method for simultaneous detection of doxorubicin and sorafenib in plasma: Application to pharmacokinetic studies in rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.Pharmaceutics · 2023Review
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- Interaction of Masitinib with Organic Cation Transporters.International journal of molecular sciences · 2022Article
- Development of UPLC-MS/MS Method to Study the Pharmacokinetic Interaction between Sorafenib and Dapagliflozin in Rats.Molecules (Basel, Switzerland) · 2022Article
- Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.The Journal of pharmacology and experimental therapeutics · 2022Article
- Transport of Drugs and Endogenous Compounds Mediated by Human OCT1: Studies in Single- and Double-Transfected Cell Models.Frontiers in pharmacology · 2021Review
- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- Substrates and Inhibitors of Organic Cation Transporters (OCTs) and Plasma Membrane Monoamine Transporter (PMAT) and Therapeutic Implications.Handbook of experimental pharmacology · 2021Article
- How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Review
- Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity.Cancers · 2020Review
- Role ofExpert opinion on drug metabolism & toxicology · 2020Review
- Molecular targeting of renal cell carcinoma by an oral combination.Oncogenesis · 2020Article
- Sorafenib Activity and Disposition in Liver Cancer Does Not Depend on Organic Cation Transporter 1.Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Sorafenib is an orally active tyrosine kinase inhibitor used in the treatment of renal and hepatocellular carcinoma. This study was designed to establish whether transport proteins are involved in the hepatic uptake of sorafenib and to determine the extent of biliary excretion of sorafenib and its metabolites in human hepatocytes. Initial uptake was assessed in freshly isolated, suspended human hepatocytes in the presence of inhibitors and modulators. [(14)C]Sorafenib (1 µM) uptake at 4°C was reduced by about 61-63% of the uptake at 37°C, suggesting a high degree of passive diffusion. Hepatocyte uptake of [(14)C]sorafenib was not Na(+) dependent or influenced by the organic anion transporter 2 inhibitor ketoprofen. However, initial [(14)C]sorafenib hepatocyte uptake was reduced by 46 and 30% compared with control values in the presence of the organic anion transporting polypeptide inhibitor rifamycin SV and the organic cation transporter (OCT) inhibitor decynium 22, respectively. [(14)C]Sorafenib (0.5-5 µM) uptake was significantly higher in hOCT1-transfected Chinese hamster ovary cells compared with mock cells, and inhibited by the general OCT inhibitor, 1-methyl-4-phenylpryidinium. OCT1-mediated uptake was saturable with a Michaelis-Menten constant of 3.80 ± 2.53 µM and a V(max) of 116 ± 42 pmol/mg/min. The biliary excretion index and in vitro biliary clearance of sorafenib (1 µM) in sandwich-cultured human hepatocytes were low (∼11% and 11 ml/min/kg, respectively). Results suggest that sorafenib uptake in human hepatocytes occurs via passive diffusion, by OCT1, and by organic anion transporting polypeptide(s). Sorafenib undergoes modest biliary excretion, predominantly as a glucuronide conjugate(s).
Indexed as
Identifiers
What OpenQuestion holds
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.