| 王倩,王彦超,董继宁,等.达沙替尼片的生物等效性研究[J].安徽医药,2024,28(9):1726-1731. |
| 达沙替尼片的生物等效性研究 |
| Study on the bioequivalence of dasatinib tablets |
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| DOI：10.3969/j.issn.1009-6469.2024.09.008 |
| 中文关键词: 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 |
| 英文关键词: Dasatinib Therapeutic equivalency Bioequivalence Liquid chromatography-tandem mass spectrometry Pharma- cokinetics Security |
| 基金项目: |
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| 摘要点击次数: 755 |
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| 中文摘要: |
| 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 WinNon- lin(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( Cmax)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( AUC0-)分别为( t242.38±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( Tmax)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 Cmax分别为( 61.86±21.90)μg/L和( 57.68±21.55)μg/L，AUC0-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，Tmax分别为( 1.74±0.80)h和( 1.61±0.88)h。两项试验 Cmax，AUC0-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。 |
| 英文摘要: |
| Objective To evaluate the bioequivalence and safety of the dasatinib tablet test preparations and the reference prepara-tions 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, two-period, crossover design was used among 52 subjects in the fasting test and 28 subjects in the postprandial test, who were randomlyassigned into two groups (T-R group and R-T group), and 50 mg of dasatinib test preparation or reference preparation was adminis-tered 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 statisti-cal analysis, and the safety of clinical observation indexes was evaluated.Results In fasting test, the Cmax of test and reference prepa-rations 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 thelast concentration can be accurately measured (AUC0-t) were (242.38±92.99) h·μg-1 ·L-1 and (241.40±82.96) h·μg-1 ·L-1, the area un- der 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 (Tmax)were (0.98±0.58) h and (0.89±0.51) h, respectively. In postprandial test, the Cmax of test and reference preparations were (61.8±21.90) μg/L and (57.68±21.55) μg/L, AUC0-t were (229.95±65.29) h·μg-1·L-1and (221.26±62.98) h·μg-1·L-1 AUC0-∞ were (238.42±66.45) h· μg-1·L-1and (229.39±65.34) h·μg-1·L-1, and Tmax were (1.74±0.80) h and (1.61±0.88) h, respectively. The 90%CI of the geometric mean ratio of Cmax, AUC0-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 reference preparation of dasatinib tablets were bioequivalent and have comparable safety underfasting and postprandial conditions. |
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