Astellas Pharma Global Development, Northbrook, IL, USA.
Astellas Research Institute of America, LLC, Northbrook, IL, USA.
Clin Drug Investig. 2020 Sep;40(9):827-838. doi: 10.1007/s40261-020-00937-z.
Methotrexate is frequently used to treat rheumatoid arthritis. Peficitinib (ASP015K; Smyraf), an oral Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis, may be coadministered with methotrexate.
The objective of this study was to investigate potential drug-drug interactions of peficitinib with methotrexate and the short-term safety of coadministration.
This phase I, open-label, single-sequence study included patients with rheumatoid arthritis taking a stable dose of methotrexate. Patients received their prescribed methotrexate dose (Day 1) and then peficitinib (100 mg) twice daily from Day 3 until the morning of Day 9; a second methotrexate dose was coadministered with peficitinib on Day 8. Serial blood samples were collected for methotrexate concentration after dosing on Days 1 (methotrexate alone) and 8 (methotrexate plus peficitinib) and for peficitinib concentration after dosing on Days 7 (peficitinib alone) and 8 (methotrexate plus peficitinib). Pre-dose concentrations of peficitinib were measured (Days 3-8).
Peficitinib concentrations reached steady state on Day 5. Administration of peficitinib did not result in changes to methotrexate area under the concentration-time curve from time zero to infinity or maximum observed concentration following a methotrexate dose (15-25 mg), and there was no significant effect of methotrexate (15-25 mg) on peficitinib area under the concentration-time curve within a 12-hour dosing interval. There were no new tolerability or safety signals after coadministration of peficitinib and methotrexate. One patient experienced two serious adverse events and withdrew from the study without receiving peficitinib.
Pharmacokinetic results showed no significant interactions between peficitinib and methotrexate. CLINICALTRIALS.
NCT01754805.
甲氨蝶呤常用于治疗类风湿关节炎。培非替尼（ASP015K；Smyraf）是一种口服 JAK 抑制剂，用于治疗类风湿关节炎，可与甲氨蝶呤联合使用。
本研究旨在探讨培非替尼与甲氨蝶呤之间的潜在药物相互作用以及联合用药的短期安全性。
这是一项 I 期、开放标签、单序列研究，纳入了正在接受稳定剂量甲氨蝶呤治疗的类风湿关节炎患者。患者在第 1 天（D1）接受了规定的甲氨蝶呤剂量，然后从第 3 天开始每天两次服用培非替尼（100mg），直至第 9 天早上；第 8 天与培非替尼同时给予第二次甲氨蝶呤剂量。在 D1（单独使用甲氨蝶呤）和 D8（甲氨蝶呤加培非替尼）给药后采集用于检测甲氨蝶呤浓度的系列血样，在 D7（单独使用培非替尼）和 D8（甲氨蝶呤加培非替尼）给药后采集用于检测培非替尼浓度的系列血样。在 D3-8 期间测量培非替尼的预剂量浓度。
培非替尼浓度于第 5 天达到稳态。培非替尼给药不会导致甲氨蝶呤的浓度-时间曲线下面积从零到无穷大或最大观察浓度发生变化，在 12 小时给药间隔内，甲氨蝶呤（15-25mg）对培非替尼的浓度-时间曲线下面积没有显著影响。培非替尼与甲氨蝶呤联合用药后无新的耐受性或安全性信号。一名患者出现 2 次严重不良事件，在未接受培非替尼治疗的情况下退出研究。
药代动力学结果表明培非替尼与甲氨蝶呤之间无显著相互作用。临床试验。
NCT01754805。
