Trial reportBritish journal of clinical pharmacology2013
Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies.
Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses 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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Efficacy and Safety of Multiple Dosages of Fostamatinib in Adult Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2019Pooled it
- Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials.Rheumatology international · 2016Pooled it
- Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies.European journal of clinical pharmacology · 2017Trial
- Characterization of the disposition of fostamatinib in Japanese subjects including pharmacokinetic assessment in dry blood spots: results from two phase I clinical studies.European journal of clinical pharmacology · 2016Trial
- B cell receptor signaling in autoimmune rheumatic diseases: regulatory mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Sol-moiety: Discovery of a water-soluble prodrug technology for enhanced oral bioavailability of insoluble therapeutics.Nature communications · 2024Article
- Pharmacological strategies for mitigating anti-TNF biologic immunogenicity in rheumatoid arthritis patients.Current opinion in pharmacology · 2023Review
- Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies.International journal of molecular sciences · 2022Review
- Drug repurposing for COVID-19 using computational screening: Is Fostamatinib/R406 a potential candidate?Methods (San Diego, Calif.) · 2022Article
- Clinical Pharmacokinetics and Pharmacodynamics of Fostamatinib and Its Active Moiety R406.Clinical pharmacokinetics · 2022Review
- Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs.International journal of molecular sciences · 2022Article
- Inhibition of Spleen Tyrosine Kinase Restores Glucocorticoid Sensitivity to Improve Steroid-Resistant Asthma.Frontiers in pharmacology · 2022Article
- Eco-Friendly UPLC-MS/MS Method for Determination of a Fostamatinib Metabolite, Tamatinib, in Plasma: Pharmacokinetic Application in Rats.Molecules (Basel, Switzerland) · 2021Article
- Syk Kinase Inhibitors Synergize with Artemisinins by Enhancing Oxidative Stress inAntioxidants (Basel, Switzerland) · 2020Article
- Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020Review
- SYK is activated by mutated MYD88 and drives pro-survival signaling in MYD88 driven B-cell lymphomas.Blood cancer journal · 2020Article
- Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA.Drugs & therapy perspectives : for rational drug selection and use · 2018Article
- Article
- Advances in the use of prodrugs for drug delivery to the eye.Expert opinion on drug delivery · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimFostamatinib (R788) is an orally dosed prodrug designed to deliver the active metabolite R940406 (R406), a spleen tyrosine kinase (SYK) inhibitor, for the treatment of rheumatoid arthritis. The objectives were to evaluate the human pharmacokinetic properties of fostamatinib and R406.
methodThree clinical studies were conducted in healthy subjects: (A) A single ascending dose study for R406 with doses ranging from 80-600 mg, (B) a single- and multiple-dose study of fostamatinib in aqueous suspension, with single doses ranging from 80-400 mg and multiple doses at 160 mg twice daily and (C) a study comparing suspension and tablet of fostamatinib, with the latter tested in both fed and fasted states.
resultsThese studies demonstrated that when administered as a solution, R406 was rapidly absorbed. Increases in exposure were observed with doses up to 400 mg. A terminal half-life of 12-21 h was observed. Similar R406 exposure could be achieved with fostamatinib suspension and steady-state was achieved after 3-4 days following twice daily administration. Fostamatinib tablet and suspension exhibited similar R406 exposure. Upon co-administration with food, a delay in peak time and lower peak concentrations of R406 were observed but at the same time the overall exposure did not change.
conclusionFostamatinib demonstrates rapid and extensive conversion to R406, an inhibitor of SYK. Solid dosage forms of fostamatinib overcome the challenge of low aqueous solubility of R406. The PK profile of R406 could potentially allow once daily or twice daily oral administration of fostamatinib.
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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.