达沙替尼片的生物等效性研究  

Study on the bioequivalence of dasatinib tablets

作　　者：王倩 王彦超 董继宁 郝颖翠 张丽丽 尹文 樊雪艳 赵可新 WANG Qian;WANG Yanchao;DONG Jining;HAO Yingcui;ZHANG Lili;YIN Wen;FAN Xueyan;ZHAO Kexin(Department of Pharmacy,Hebei PetroChina Central Hospital,Langfang,Hebei 065000,China)

机构地区：[1]河北中石油中心医院药学部,河北廊坊065000

出　　处：《安徽医药》2024年第9期1726-1731,共6页Anhui Medical and Pharmaceutical Journal

摘　　要：目的评价达沙替尼片受试制剂与参比制剂在中国健康受试者空腹和餐后状态下的生物等效性和安全性。方法于2020年12月至2021年2月在河北中石油中心医院,采用单中心、单次给药、随机、开放、两制剂、两周期、交叉设计,空腹试验52例受试者,餐后试验28例受试者按随机数字表法分为两组[受试制剂(T)-参比制剂(R)组,R-T组],每周期给药1次,每次服用50 mg达沙替尼片受试制剂或参比制剂,采用液相色谱-串联质谱(LC-MS/MS)法测定达沙替尼的血药浓度,由Phoenix WinNonlin(8.2版本)或SAS(9.4版本)软件,非房室模型计算药动学参数,进行统计分析,并对受试者的临床观察指标进行安全性评价。结果空腹试验受试制剂和参比制剂的药峰浓度(C_(max))分别为(97.76±44.25)μg/L和(98.59±43.34)μg/L,从0时至最后一个时间点的药时曲线下面积(AUC_(0-t))分别为(242.38±92.99)h·μg^(−1)·L^(−1)和(241.40±82.96)h·μg^(−1)·L^(−1),从0时至无限时间的药时曲线下面积(AUC0-∞)分别为(248.87±93.38)h·μg^(−1)·L^(−1)和(248.85±81.84)h·μg^(−1)·L^(−1),达峰时间(T_(max))分别为(0.98±0.58)h和(0.89±0.51)h。餐后试验受试制剂和参比制剂的C_(max)分别为(61.86±21.90)μg/L和(57.68±21.55)μg/L,AUC_(0-t)分别为(229.95±65.29)h·μg^(−1)·L^(−1)和(221.26±62.98)h·μg^(−1)·L^(−1);AUC0-∞分别为(238.42±66.45)h·μg^(−1)·L^(−1)和(229.39±65.34)h·μg^(−1)·L^(−1),T_(max)分别为(1.74±0.80)h和(1.61±0.88)h。两项试验C_(max),AUC_(0-t),AUC0-∞几何均值比的90%CI为80%~125%。整个试验过程中未发生严重不良事件。结论空腹、餐后条件下,达沙替尼片受试制剂和参比制剂生物等效,安全性相当。Objective To evaluate the bioequivalence and safety of the dasatinib tablet test preparations and the reference preparations in the fasting and postprandial conditions in the healthy Chinese subjects.Methods This study was conducted at Hebei Petro‐China Central Hospital from December 2020 to February 2021.A single-center,single-dose,randomized,open,two-preparation,twoperiod,crossover design was used among 52 subjects in the fasting test and 28 subjects in the postprandial test,who were randomly assigned into two groups(T-R group and R-T group),and 50 mg of dasatinib test preparation or reference preparation was administered once per period.The plasma concentration of dasatinib was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters were calculated by Phoenix WinNonlin(version 8.2)or SAS(version 9.4)for statistical analysis,and the safety of clinical observation indexes was evaluated.Results In fasting test,the C_(max)of test and reference preparations were(97.76±44.25)μg/L and(98.59±43.34)μg/L,the area under the curve from 0 to the sample collection time t when the last concentration can be accurately measured(AUC_(0-t))were(242.38±92.99)h·μg^(−1)·L^(−1)and(241.40±82.96)h·μg^(−1)·L^(−1),the area under the curve from 0 to infinite time(AUC0-∞)were(248.87±93.38)h·μg^(−1)·L^(−1)and(248.85±81.84)h·μg^(−1)·L^(−1),and time to peak(T_(max))were(0.98±0.58)h and(0.89±0.51)h,respectively.In postprandial test,the C_(max)of test and reference preparations were(61.8±21.90)μg/L and(57.68±21.55)μg/L,AUC_(0-t)were(229.95±65.29)h·μg^(−1)·L^(−1)and(221.26±62.98)h·μg^(−1)·L^(−1)AUC0-∞were(238.42±66.45)h·μg^(−1)·L^(−1)and(229.39±65.34)h·μg^(−1)·L^(−1),and T_(max)were(1.74±0.80)h and(1.61±0.88)h,respectively.The 90%CI of the geometric mean ratio of C_(max),AUC_(0-t)and AUC0-∞in the two tests was 80%-125%.No serious adverse events occurred during the whole test.Con⁃clusion The test preparation and

关 键 词：达沙替尼 治疗等效 生物等效 液相色谱-串联质谱 药代动力学 安全性 

分 类 号：R969.4[医药卫生—药理学]