Astellas Pharma Global Development Inc., Northbrook, IL, USA.
California Clinical Trials, PAREXEL International, Glendale, CA, USA.
Clin Pharmacol Drug Dev. 2017 Nov;6(6):548-555. doi: 10.1002/cpdd.344. Epub 2017 Mar 16.
Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14. Repeated-dose administration of verapamil increased mean peficitinib AUC , AUC , and C by 27%, 27%, and 39%, respectively, and also increased the mean AUC and C of peficitinib metabolites H1, H2, and H4. Coadministration of verapamil with peficitinib 150 mg was generally well tolerated. Overall, the most commonly reported adverse event was headache, which occurred in 5 subjects (21%); all reported adverse events were grade 1 severity, with the exception of 1 grade 2 incident of vomiting.
培非替尼是一种每日口服一次的 Janus 激酶抑制剂，目前正在开发用于治疗类风湿关节炎。体外研究表明，培非替尼是 P 糖蛋白（P-gp）的底物。本开放标签、单中心、单序列、交叉药物相互作用研究评估了 P-gp 外排泵抑制剂维拉帕米对培非替尼药代动力学特征的影响。24 名健康志愿者在 14 天治疗期的第 1 天和第 12 天接受单次 150mg 培非替尼剂量，在第 5-14 天每天接受维拉帕米 80mg，每日 3 次。重复给予维拉帕米使培非替尼的平均 AUC 、 AUC 和 C 分别增加了 27%、27%和 39%，同时还增加了培非替尼代谢物 H1、H2 和 H4 的平均 AUC 和 C。培非替尼 150mg 与维拉帕米联合使用通常具有良好的耐受性。总体而言，最常报告的不良事件是头痛，有 5 名受试者（21%）发生；所有报告的不良事件均为 1 级严重程度，除 1 例 2 级呕吐事件外。
