维格列汀片空腹人体生物等效性研究

Bioequivalence of vildagliptin tablets in healthy volunteers

目的:评价2种维格列汀片在中国健康人体内的生物等效性及安全性。方法:采用单剂量、随机、开放的两周期双交叉试验设计(清洗期为7 d)。36例健康成人受试者随机分成2组,分别空腹给予国产维格列汀片(受试制剂)或进口维格列汀片(参比制剂)50 mg。按预定时间点采集血样,离心后取血浆于-70℃冰箱储存。采用HPLC-MS/MS法测定血浆中维格列汀的浓度,绘制药时曲线,进行药动学参数计算和生物等效性评价。受试者试验期间置于Ⅰ期病房,由研究医生及研究护士全程监护,记录受试者给药后的生命体征和不良事件,试验前及试验完成后分别进行体格检查与实验室检查。结果:实际入组36例受试者中,1例因用药前不良事件退出,其余35例完成试验。受试制剂和参比制剂Cmax,AUC0~t和AUC0~∞的几何均值比的90%置信区间分别为94.32%~108.68%,99.13%~103.72%和99.38%~104.06%,均符合生物等效性的等效范围要求(80.00%~125.00%)。试验过程中,7例受试者报告轻度不良事件,未发生严重不良事件。结论:2种维格列汀片制剂生物等效,在健康受试者体内安全、耐受。

Objective： To evaluate the bioequivalence and safety of two kinds of vildagliptin tablets in healthy Chinese volunteers. Methods： A randomized,single-dosed,open label,two way crossover study was designed（ cleanse time is seven days）. Thirty-six healthy adult volunteers were randomly divided into two groups and administered with single dose of test or reference preparation of vildagliptin tablets（ 50 mg） respectively under the condition of fasting. Blood samples were collected at due time. Plasma was then obtained and stored at-70 ℃refrigerator after centrifugation. HPLC-MS/MS was applied to determine the concentration of vildagliptin in plasma,and the drug and time curve was drew to calculate the pharmacokinetic parameters and to evaluate the bioequivalence.All subjects were housed in Phase I wards and were monitored intensively by doctors or nurses. Vital signs and adverse events（ AEs） after medication were recorded, and physical examination and laboratory tests were performed before and after the completion of the trial. Results： Thirty-six subjects were enrolled in the study with one subject withdrawn from the trial by adverse events before treatment. The remaining thirty-five subjects completed the trial. The 90% confidential intervals（ CIs） for the ratios of Cmax,AUC0 - tand AUC0 - ∞were 94. 32% -108. 68%,99. 13% - 103. 72% and 99. 38% - 104. 06%,respectively,which all met the predetermined criteria for assuming bioequivalence（ 80. 00% - 125. 00%）. Seven subjects reported mild AEs; no serious adverse events（ SAEs） were observed. Conclusion： Both the test and reference preparations of vildagliptin tablets are safe and tolerated,which met the regulatory definition for assuming bioequivalence in Chinese healthy adult volunteers.