他米巴罗汀片在复发急性早幼粒细胞白血病患者的药代动力学研究  

Pharmacokinetics of tamibarotene tablets in Chinese patients with recurrent acute promyelocytic leukemia

作　　者：孙明媛 宫本法 秘营昌 王建祥 向瑾[2] SUN Ming-yuan;XIANG Jin;GONG Ben-fa;MI Ying-chang;WANG Jian-xiang(PhaseⅠClinical Trail Unit,State Key Laboratory of Experimental Hematology,National Clinical Research Center for Hematological Disorders,Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300020,China;PhaseⅠClinical Research Unit,West China Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]中国医学科学院血液病医院、中国医学科学院血液学研究所、实验血液学国家重点实验室、国家血液系统疾病临床医学研究中心Ⅰ期临床研究病房,天津300020 [2]四川大学华西医院Ⅰ期临床研究室,四川成都610041

出　　处：《中国临床药理学杂志》2021年第12期1581-1585,共5页The Chinese Journal of Clinical Pharmacology

基　　金：重大新药创制国家科技重大专项基金资助项目(2017ZX09304024)。

摘　　要：目的探索他米巴罗汀片在中国复发急性早幼粒细胞白血病(APL)患者体内的药代动力学特征。方法按开放、多中心非随机试验设计。10例患者给予他米巴罗汀(6 mg·m^(-2)·d^(-1))分2次于每日早、晚餐后1 h内口服,服药间隔为12 h,第2天开始联合三氧化二砷静脉滴注治疗,其中第1,14天他米巴罗汀仅于早餐后口服。用HPLC-MS/MS法测定血药浓度,用PhoenixTMWin Nonlin?6.1计算药代动力学参数。结果单次及多次给药后,他米巴罗汀的主要药代动力学参数:Cmax分别为(62.44±22.22)和(56.87±17.72)ng·m L^(-1),AUC0-t分别为(341.51±149.16)和(286.27±112.68)ng·m L^(-1)·h,t1/2分别为(3.65±1.62)和(4.82±2.66)h。结论10例APL受试者单次和多次口服他米巴罗汀后的体内变化规律一致。Objective To evaluate the pharmacokinetics of tamibarotene tablets in patients with recurrent acute promyelocytic leukemia(APL).Methods An open,multi-center and no-randomized study was conducted.The blood drug concentration of oral tamibarotene in 10recurrent APL patients were studied by HPLC-MS/MS after single or multiple doses.Tamibarotene(6 mg·m^(-2)·d^(-1))was taken orally within 1 hour after breakfast and dinner every day,with intervals of 12hours.Combination therapy with intravenous arsenic trioxide was given on the second day.On day 1 and day 14,tamibarotene was taken orally only once after breakfast.Calculation of pharmacokinetic parameters of tamibarotene with PhoenixTM Win Nonlin?6.1.Results The major pharmacokinetic parameters after single and multiple doses were as follows:Cmax were(62.44±22.22)and(56.87±17.72)ng·m L^(-1),AUC0-twere(341.51±149.16)and(286.27±112.68)ng·m L^(-1)·h,t1/2 were(3.65±1.62)and(4.82±2.66)h.Conclusion The change trend of tamibarotene after single and multiple oral administration was consistent.

关 键 词：他米巴罗汀 急性早幼粒细胞白血病 药代动力学 

分 类 号：R97[医药卫生—药品]