Trial reportInvestigational new drugs2012
Plasma protein binding of sorafenib, a multi kinase inhibitor: in vitro and in cancer patients.
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.
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
26 citing papers in PubMed, 54 citations in OpenAlex.
- Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.Clinical pharmacology and therapeutics · 2014Trial
- Tumor-Targeted Delivery of an EGFR Inhibitor Prodrug via Site-Specific Albumin Conjugation.Journal of medicinal chemistry · 2026Article
- Predictive value of the serum albumin change rate for therapeutic response to targeted therapy in patients with AIDS-related non-Hodgkin lymphoma.Frontiers in nutrition · 2025Article
- Parenteral Nanoemulsions Loaded with Combined Immuno- and Chemo-Therapy for Melanoma Treatment.Nanomaterials (Basel, Switzerland) · 2022Article
- EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function.BMC cancer · 2021Article
- In vivo assessment of the drug interaction between sorafenib and paracetamol in rats.Cancer chemotherapy and pharmacology · 2020Article
- Sorafenib Loaded Inhalable Polymeric Nanocarriers against Non-Small Cell Lung Cancer.Pharmaceutical research · 2020Article
- A Prospective Study of Peritransplant Sorafenib for Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020Article
- Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment.International journal of molecular sciences · 2019Review
- Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma.Clinical pharmacokinetics · 2019Review
- Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure-FLT3 Relationship.Clinical and translational science · 2018Article
- Effect of tyrosine kinase inhibitors on renal handling of creatinine by MATE1.Scientific reports · 2018Article
- Hepatocellular carcinoma-associated hypercholesterolemia: involvement of proprotein-convertase-subtilisin-kexin type-9 (PCSK9).Cancer & metabolism · 2018Article
- Limited Tumor Tissue Drug Penetration Contributes to Primary Resistance against Angiogenesis Inhibitors.Theranostics · 2017Article
- Patient-Level Adverse Event Patterns in a Single-Institution Study of the Multi-Kinase Inhibitor Sorafenib.Clinical and translational science · 2016Article
- A high-content EMT screen identifies multiple receptor tyrosine kinase inhibitors with activity on TGFβ receptor.Oncotarget · 2016Article
- Determination of unbound fraction of pazopanib in vitro and in cancer patients reveals albumin as the main binding site.Investigational new drugs · 2016Article
- Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer.Scientific reports · 2016Article
- Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology.NPJ systems biology and applications · 2015Article
- Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells.Journal of cellular physiology · 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
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Sorafenib is an orally administered multikinase inhibitor that exhibits antiangiogenic and antitumor activity. Few investigators have been able to correlate cumulative sorafenib dose or total exposure to pharmacodynamic effects. This discrepancy may be in part due to poorly understood protein binding characteristics. Since unbound drug concentrations are believed to be more relevant to pharmacological and toxicological responses than total drug, an equilibrium dialysis method using 96-well microdialysis plates was optimized and validated for determining the fraction unbound (F(u)) sorafenib in human plasma and in isolated protein solutions. Unbound sorafenib concentrations were determined in cancer patients receiving the drug orally at a dose of 400 mg and 600 mg twice daily. Sorafenib was extensively bound with mean F(u) value of 0.3% in both non-cancer and cancer patient's plasma. The binding in plasma was concentration independent, indicating a low-affinity, possibly nonspecific and nonsaturable process. In isolated protein solutions, 99.8% and 79.3% of sorafenib was bound to human serum albumin (HSA) (4 g/dL) and α(1)-acid glycoprotein (AAG) (0.1 g/dL) with binding constants of 1.24 × 10(6) M(-1) and 1.40 × 10(5) M(-1), respectively. In cancer patients receiving sorafenib, unbound sorafenib was not correlated with patient characteristics or laboratory values. In conclusion, sorafenib is highly protein bound in human plasma with a higher affinity towards albumin and limited free drug may be partly responsible for its borderline clinical activity.
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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.