Abstract | AIM: METHOD: Three 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. RESULTS: These 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. CONCLUSION:
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Authors | Muhammad Baluom, Elliott B Grossbard, Tim Mant, David T W Lau |
Journal | British journal of clinical pharmacology
(Br J Clin Pharmacol)
Vol. 76
Issue 1
Pg. 78-88
(Jul 2013)
ISSN: 1365-2125 [Electronic] England |
PMID | 23190017
(Publication Type: Clinical Trial, Phase I, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 Rigel Pharmaceuticals, Inc.. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society. |
Chemical References |
- Aminopyridines
- Intracellular Signaling Peptides and Proteins
- Morpholines
- N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine
- Oxazines
- Pharmaceutical Solutions
- Prodrugs
- Protein Kinase Inhibitors
- Pyridines
- Pyrimidines
- Suspensions
- Tablets
- Protein-Tyrosine Kinases
- SYK protein, human
- Syk Kinase
- fostamatinib
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Topics |
- Administration, Oral
- Adolescent
- Adult
- Aminopyridines
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Administration Schedule
- Female
- Food-Drug Interactions
- Half-Life
- Humans
- Intracellular Signaling Peptides and Proteins
(antagonists & inhibitors)
- Male
- Middle Aged
- Morpholines
- Oxazines
(administration & dosage, pharmacokinetics)
- Pharmaceutical Solutions
- Prodrugs
- Protein Kinase Inhibitors
(administration & dosage, pharmacokinetics)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Pyridines
(administration & dosage, pharmacokinetics)
- Pyrimidines
- Suspensions
- Syk Kinase
- Tablets
- Young Adult
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