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Fostamatinib, a Syk‐Kinase Inhibitor, Does Not Affect Methotrexate Pharmacokinetics in Patients With Rheumatoid Arthritis
Author(s) -
Baluom Muhammad,
Samara Emil,
Grossbard Elliott B.,
Lau David T.W.
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010381496
Subject(s) - rheumatoid arthritis , pharmacokinetics , methotrexate , medicine , pharmacology , placebo , arthritis , gastroenterology , active metabolite , area under the curve , alternative medicine , pathology
Fostamatinib (R788) is being investigated as an add‐on therapy for the treatment of rheumatoid arthritis (RA) in patients with inadequate response to methotrexate (MTX). This study evaluated the potential pharmacokinetic interaction between R788 and MTX. Sixteen RA subjects on a stable weekly MTX regimen were enrolled and received MTX on days 1 and 8. Twelve subjects received 100 mg of R788 orally, and 4 subjects received a matching placebo twice daily from days 4 to 8 and once daily on days 3 and 9. Blood samples were collected on days 1 and 8 for MTX and 7‐hydroxymethotrexate (7‐OH‐MTX), and days 3 and 9 for R788 and its active metabolite, R406. MTX and 7‐OH‐MTX pharmacokinetic parameters were similar on days 1 and 8. In the R788 group, the mean day 8 to day 1 ratios (90% confidence intervals) of maximum concentration and area under the plasma concentration—time curve estimates were 1.01 (0.85–1.20) and 1.12 (0.90–1.40) for MTX and 1.06 (0.82–1.35) and 1.06 (0.83–1.36) for 7‐OH‐MTX, respectively. Urinary excretion of MTX and 7‐OH‐MTX was also similar with or without R788, averaging 58% to 69% and 4% to 5% of the MTX dose, respectively. The data suggest that there is no clinically significant pharmacokinetic interaction of R788 and MTX in RA patients.