Trial reportInvestigational new drugs2012
Saturable absorption of sorafenib in patients with solid tumors: a population model.
Trial report in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Pooled it
- Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.Clinical pharmacology and therapeutics · 2014Trial
- Sorafenib in advanced melanoma: a critical role for pharmacokinetics?British journal of cancer · 2012Trial
- Article
- Upholding or Breaking the Law of Superposition in Pharmacokinetics.Biomedicines · 2024Review
- A PK-PD model linking biomarker dynamics to progression-free survival in patients treated with everolimus and sorafenib combination therapy, EVESOR phase I trial.Cancer chemotherapy and pharmacology · 2023Article
- Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cancer.Cancers · 2023Review
- Enhanced oral bioavailability and antitumor therapeutic efficacy of sorafenib administered in core-shell protein nanoparticle.Drug delivery and translational research · 2022Article
- Relevance of Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in Routine Clinical Practice: A Pilot Study.Pharmaceutics · 2022Article
- Pharmacokinetically guided dosing of oral sorafenib in pediatric hepatocellular carcinoma: A simulation study.Clinical and translational science · 2021Article
- Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC.Pharmaceuticals (Basel, Switzerland) · 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
- 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 landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.Expert review of anticancer therapy · 2019Review
- Body Composition Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma Treated with Sorafenib.Liver cancer · 2019Article
- Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure-FLT3 Relationship.Clinical and translational science · 2018Article
- The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism.Pharmaceutical biology · 2017Article
- The cutting edge of metastatic melanoma therapy.Melanoma management · 2016Review
- Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma.Cancer research · 2015Article
- Measurement of sorafenib plasma concentration by high-performance liquid chromatography in patients with advanced hepatocellular carcinoma: is it useful the application in clinical practice? A pilot study.Medical oncology (Northwood, London, England) · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is an oral tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. By using a population approach, this study aimed to characterise its pharmacokinetics. Plasma concentration-time data (n = 372) from 71 patients under sorafenib were analysed using nonlinear mixed-effect modelling to estimate population pharmacokinetic parameters, as well as relationships between these parameters and different covariates (demographic, biological). Simulations were done to compare different daily dosing regimens in a context of dose-escalation. A 1-compartment model with saturated absorption, first-order intestinal loss and elimination best described the pharmacokinetics of sorafenib. Absolute bioavailability significantly dropped with increasing daily doses of sorafenib. AUC increased less than proportionally with increasing doses [47.3 (41.3-63.3), 60.3 (56.3-64.4), 71.4 (51.3-99.1), 75.9 (45.5-100.9) mg/L.h for 400, 800, 1,200 and 1,600 mg/day, respectively]. According to the simulations, dividing the daily dose in three or four doses for daily dose >800 mg would significantly increase AUC compared with a twice daily dosing regimen (101.7 vs 81.6 mg/L.h for 400 mg q8h and 600 mg q12h respectively; 131.6 vs 91.5 mg/L.h for 400 mg q6h and 800 mg q12h, respectively). Thrice daily regimen may be most suitable in a context of dose-escalation (>800 mg/day) in non-responders to standard-dosing regimen.
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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.