ArticleCancer chemotherapy and pharmacology2016
Sorafenib metabolism, transport, and enterohepatic recycling: physiologically based modeling and simulation in mice.
Article in Cancer chemotherapy and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 50 citations in OpenAlex.
- Immune-Evasive Biomimetic Gold-Carbon Nanoplatform for Dual-Modal Theranostics of Hepatocellular Carcinoma.Small methods · 2026Article
- The gut microbiota: an emerging modulator of drug resistance in hepatocellular carcinoma.Gut microbes · 2025Review
- Predicting tumor dynamics in treated patients from patient-derived-xenograft mouse models: a translational model-based approach.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Decoding Drug Interactions: Character and Degree of Pharmacokinetic Interactions Between Telmisartan and Sorafenib or Donafenib in Rats.Drug design, development and therapy · 2025Article
- Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.Acta pharmaceutica Sinica. B · 2024Article
- Pharmacokinetic Simulation and Area under the Curve Estimation of Drugs Subject to Enterohepatic Circulation.Pharmaceutics · 2024Article
- A real-world pharmacovigilance study of Sorafenib based on the FDA Adverse Event Reporting System.Frontiers in pharmacology · 2024Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma.Pharmaceutics · 2022Article
- The role of gut microbial β-glucuronidase in drug disposition and development.Drug discovery today · 2022Review
- Pharmacokinetic Interactions between Canagliflozin and Sorafenib or Lenvatinib in Rats.Molecules (Basel, Switzerland) · 2022Article
- A PBPK model recapitulates early kinetics of anti-PEG antibody-mediated clearance of PEG-liposomes.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Microvesicles: the functional mediators in sorafenib resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- A Novel Integrated Pharmacokinetic-Pharmacodynamic Model to Evaluate Combination Therapy and DetermineThe Journal of pharmacology and experimental therapeutics · 2021Article
- Elucidating the Molecular Basis of Sorafenib Resistance in HCC: Current Findings and Future Directions.Journal of hepatocellular carcinoma · 2021Review
- Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption.Frontiers in pharmacology · 2021Article
- Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study.Cancer chemotherapy and pharmacology · 2020Article
- Targeting Regorafenib-Induced Toxicity through Inhibition of Gut Microbial β-Glucuronidases.ACS chemical biology · 2019Article
- Sorafenib Population Pharmacokinetics and Skin Toxicities in Children and Adolescents with Refractory/Relapsed Leukemia or Solid Tumor Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeThis study used uncertainty and sensitivity analysis to evaluate a physiologically based pharmacokinetic (PBPK) model of the complex mechanisms of sorafenib and its two main metabolites, sorafenib glucuronide and sorafenib N-oxide in mice.
methodsA PBPK model for sorafenib and its two main metabolites was developed to explain disposition in mice. It included relevant influx (Oatp) and efflux (Abcc2 and Abcc3) transporters, hepatic metabolic enzymes (CYP3A4 and UGT1A9), and intestinal β-glucuronidase. Parameterization of drug-specific processes was based on in vitro, ex vivo, and in silico data along with plasma and liver pharmacokinetic data from single and multiple transporter knockout mice.
resultsUncertainty analysis demonstrated that the model structure and parameter values could explain the observed variability in the pharmacokinetic data. Global sensitivity analysis demonstrated the global effects of metabolizing enzymes on sorafenib and metabolite disposition and the local effects of transporters on their respective substrate exposures. In addition, through hypothesis testing, the model supported that the influx transporter Oatp is a weak substrate for sorafenib and a strong substrate for sorafenib glucuronide and that the efflux transporter Abcc2 is not the only transporter affected in the Abcc2 knockout mouse.
conclusionsTranslation of the mouse model to humans for the purpose of explaining exceptionally high human pharmacokinetic variability and its relationship with exposure-dependent dose-limiting toxicities will require delineation of the importance of these processes on disposition.
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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.