Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2012
Ontogeny and sorafenib metabolism.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 43 citations in OpenAlex.
- Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide.Clinical and translational science · 2017Trial
- Prospective analysis of tiopronin in prevention of sorafenib and antiviral therapy inducing liver toxicity in advanced hepatitis B virus-related hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2015Trial
- Trial
- Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Role of Genetic Polymorphisms in Drug-Metabolizing Enzyme-Mediated Toxicity and Pharmacokinetic Resistance to Anti-Cancer Agents: A Review on the Pharmacogenomics Aspect.Clinical pharmacokinetics · 2022Review
- Microvesicles: the functional mediators in sorafenib resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer-Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension.International journal of molecular sciences · 2021Review
- Upregulation of lncRNA NIFK-AS1 in hepatocellular carcinoma by mHuman cell · 2021Review
- m6A RNA methylation-mediated HNF3γ reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance.Signal transduction and targeted therapy · 2020Article
- UDP-glucuronosyltransferase polymorphisms affect diethylnitrosamine-induced carcinogenesis in humanized transgenic mice.Cancer science · 2020Article
- PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Sorafenib Activity and Disposition in Liver Cancer Does Not Depend on Organic Cation Transporter 1.Clinical pharmacology and therapeutics · 2020Article
- 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
- The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism.Pharmaceutical biology · 2017Article
- Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats.Molecules (Basel, Switzerland) · 2017Article
- Sorafenib metabolism, transport, and enterohepatic recycling: physiologically based modeling and simulation in mice.Cancer chemotherapy and pharmacology · 2016Article
- Immunohistochemical markers of CYP3A4 and CYP3A7: a new tool towards personalized pharmacotherapy of hepatocellular carcinoma.European journal of histochemistry : EJH · 2016Article
- Article
- Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b.Cancer research · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo investigate the role of ontogeny in sorafenib metabolism to the equipotent active metabolite sorafenib N-oxide. EXPERIMENTAL
designSteady-state pharmacokinetic studies of sorafenib and metabolites were conducted in 30 children and young adults (17 males; median age, 9.5 years) receiving sorafenib 150 mg/m(2) or 200 mg/m(2) twice daily. Sorafenib metabolism was evaluated in vitro at 10 μmol/L using a panel of purified human cytochrome P450 (CYP) enzymes. Sorafenib metabolism and CYP3A4 expression was evaluated in 52 human liver samples from donors of ≤20 years old. The drug-drug interaction potential between sorafenib and azole antifungal agents was evaluated in vitro and in vivo.
resultsNo age-related differences in sorafenib apparent oral clearance were observed. Mean sorafenib N-oxide metabolite ratio was 0.27 ± 0.14. In children of ≤10 years of age, boys had approximately 2-fold higher N-oxide ratios than girls (0.40 ± 0.15 vs. 0.22 ± 0.12, P = 0.026). Of the CYPs evaluated, sorafenib was exclusively metabolized to sorafenib N-oxide by CYP3A4. A trend for increased N-oxide formation in boys was observed in liver samples, which correlated with CYP3A4 mRNA expression. Posaconazole and voriconazole potently inhibited sorafenib N-oxide formation in vitro, and reduced sorafenib N-oxide formation in 3 children given sorafenib concurrent with azoles.
conclusionWe have identified several factors affecting interpatient variability in sorafenib metabolism to the active N-oxide metabolite including age, sex, and concurrent treatment with azole antifungals. This knowledge may provide important considerations for the clinical use of sorafenib in children and possibly other kinase inhibitors undergoing CYP3A4-mediated metabolism.
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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.