法米替尼治疗晚期实体瘤患者的药代动力学及安全性  

Pharmacokinetics and safety of famitinib in the treatment of patients with advanced solid tumors

作　　者：唐银梅 冯元莹 白桂颖 王璇 赵伟鹏 张杰 史业辉 TANG Yinmei;FENG Yuanying;BAI Guiying;WANG Xuan;ZHAO Weipeng;ZHANG Jie;SHI Yehui(Department of Breast Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin′s Clinical Research Center for Cancer,Key Laboratory of Breast Cancer Prevention and Therapy,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院乳腺内科,国家恶性肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心,乳腺癌防治教育重点实验室,天津300060

出　　处：《天津医科大学学报》2024年第1期84-88,共5页Journal of Tianjin Medical University

基　　金：天津市教委科研计划项目(2016YD03)。

摘　　要：目的:研究法米替尼15、20、25 mg剂量组在晚期实体瘤患者的药代动力学特征和安全性。方法:32例晚期或转移的实体瘤患者接受15、20、25 mg/d治疗,比较每个剂量组单次给药和多次给药后原型药物法米替尼及代谢物SHR116637的达峰时间(T_(max))、血药峰浓度(C_(max))等相关药代动力学的参数变化,观察治疗期间法米替尼在实体瘤患者中的不良事件/严重不良事件的发生率。结果:各剂量组单次给药后,血浆中法米替尼和代谢物SHR116637在6 h达峰,低、中、高剂量组t_(1/2)分别为(73.6±12.3)、(75.8±17.0)、(65.8±23.8)h;代谢物SHR116637的体内暴露量AUC_(0-24)、AUC_(0-t)和AUC_(0-∞)均随剂量增加而增加。多次给药后血浆中法米替尼及代谢物SHR116637 T_(max)与单次给药相比略有延迟。多次给药后法米替尼和代谢物SHR116637均有一定程度的蓄积,但以代谢物SHR116637中15 mg剂量组最明显,蓄积指数R_(AC_AUC)和R_(AC_Cmax)分别为6.45±2.82和5.37±2.39。单次给药阶段受试者无严重不良事件发生;在多次给药阶段共有2例受试者发生呼吸衰竭和心力衰竭。结论:单次给药后法米替尼在体内分布很广且消除较慢;多次给药后代谢物SHR116637有一定蓄积,3种剂量的法米替尼的安全性和耐受性良好。Objective:To investigate the pharmacokinetic profile and safety of the 15,20,and 25 mg dose groups of famitinib in patients with advanced solid tumors.Methods:Thirty-two patients with progressive or metastatic solid tumors were treated with 15,20,or 25 mg/d.The changes in parameters associated to pharmacokinetics such as time to peak(T_(max))and peak blood concentration(C_(max))of the prototype drug famitinib and metabolite SHR116637 were compared after single and multiple dosing in each dose group.The incidence of adverse events/serious adverse events with famitinib in patients with solid tumors during treatment was observed.Results:After a single administration in each dose group,famitinib and metabolite SHR116637 in plasma peaked at 6 h,and the T_(1/2) in the low-,medium-,and high-dose groups were(73.6±12.3),(75.8±17.0),and(65.8±23.8)h,respectively.The in vivo exposure of metabolite SHR116637 AUC_(0-24),AUC_(0-t),and AUC_(0-∞) all increased with increasing dose.The median T_(max) of famitinib and metabolite SHR116637 in plasma after multiple administrations was slightly delayed compared to a single administration.After multiple doses,there was an accumulation of famitinib and its metabolite SHR116637.The accumulation was most noticeable in the group that received 15 mg of the metabolite SHR116637.The accumulation indices R_(AC-AUC) and R_(AC-Cmax) were 6.45±2.82 and 5.37±2.39,respectively.No serious adverse events occurred in subjects during the single-dose phase;a total of 2 subjects experienced respiratory failure and heart failure during the multiple-dose phase.Conclusion:Famitinib is widely distributed and slowly eliminated in the body after a single dose.Following multiple administrations,metabolite SHR116637 has a certain accumulation.The safety and tolerance of all three doses of famitinib are good.

关 键 词：法米替尼 晚期实体瘤 药代动力学 安全性 

分 类 号：R73[医药卫生—肿瘤]