Rigel Pharmaceuticals, Inc, 1180 Veterans Blvd., South San Francisco, CA 94080, USA.
J Clin Pharmacol. 2011 Sep;51(9):1310-8. doi: 10.1177/0091270010381496. Epub 2011 Jan 5.
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.
福他替尼（R788）正在被研究作为一种附加疗法，用于治疗对甲氨蝶呤（MTX）反应不足的类风湿关节炎（RA）患者。这项研究评估了 R788 与 MTX 之间潜在的药代动力学相互作用。16 名正在接受稳定每周 MTX 方案治疗的 RA 患者参与了该研究，并在第 1 天和第 8 天接受 MTX 治疗。12 名患者口服 100mg R788，4 名患者在第 4 天至第 8 天每天接受两次安慰剂，并在第 3 天和第 9 天每天接受一次安慰剂。在第 1 天和第 8 天采集 MTX 和 7-羟甲氨蝶呤（7-OH-MTX）的血样，在第 3 天和第 9 天采集 R788 和其活性代谢物 R406 的血样。第 1 天和第 8 天的 MTX 和 7-OH-MTX 药代动力学参数相似。在 R788 组中，第 8 天到第 1 天的最大浓度和血浆浓度-时间曲线下面积的比值（90%置信区间）分别为 MTX 的 1.01（0.85-1.20）和 1.12（0.90-1.40），7-OH-MTX 的 1.06（0.82-1.35）和 1.06（0.83-1.36）。无论是否使用 R788，MTX 和 7-OH-MTX 的尿液排泄量也相似，分别为 MTX 剂量的 58%至 69%和 4%至 5%。数据表明，在 RA 患者中，R788 与 MTX 之间没有临床意义上的药代动力学相互作用。
