甲磺酸伊马替尼片在中国健康志愿者中一项开放、随机、双周期交叉生物等效性试验研究

An Open,Randomized,Biperiodic,Crossover Bioequivalence Study of Imatinib Mesylate Tablets in Chinese Healthy Volunteers

目的评价受试制剂(甲磺酸伊马替尼片,400 mg)与参比制剂(甲磺酸伊马替尼片,GLEEVEC·,400 mg)餐后口服给药在健康成年志愿者中的生物等效性。方法采用随机、开放、单剂量、两制剂、两序列、两周期、交叉设计方法,将24例志愿者随机分为两组,单次服用受试制剂T和参比制剂R。采用高效液相色谱-串联质谱(LC-MS/MS)测定血浆中伊马替尼的浓度;采用非房室模型,利用WinNonlin·7.0软件进行药动学参数的计算。结果甲磺酸伊马替尼片参比制剂与受试制剂的主要药代动力学参数Cmax分别为(2383.33±770.68)ng·mL-1、(2498.00±708.78)ng·mL-1;Tmax分别为3.00 h、2.75 h;T1/2分别为(14.23±1.9)h、(14.33±1.76)h;AUC0-t分别为(40 267.24±14 685.17)ng·mL-1·h、(41 167.68±13 947.54)ng·mL-1·h;AUC0-∞分别为(41 492.96±15 231.43)ng·mL-1·h、(42 392.65±14 397.83)ng·mL-1·h;两种制剂的 AUC0-t、AUC0-∞及Cmax经对数转换后,90%可信区间(90% CI)分别为91.77%~102.20%、91.74%~102.28%、94.46%~106.53%。受试制剂对于参比制剂的平均生物利用度AUC0-t为(97.12±1.22)%,AUC0-∞为(97.15±1.17)%,均>90%。结论受试制剂与参比制剂餐后口服给药具有生物等效性。

Objective To evaluate the bioequivalence of test imatinib mesylate tablet (400 mg) and the reference imatinib mesylate tablet (GLEEVEC ,400 mg) in healthy Chinese adult volunteers on postprandial state.Methods Twenty-four volunteers were randomly divided into two groups by random,open,single-dose,two-preparation,two-sequence,and two-cycle design methods.They were given either the test preparation or the reference preparation.The plasma concentration of imatinib was determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).Non-atrioventricular model and WinNonlin 7.0 software were used for calculating pharmacokinetic parameters.Results The Cmax of test and reference imatinib mesylate tablets were (2383.33±770.68) ng?mL-1and (2498.00±708.78) ng?mL-1 respectively.Tmax were 3.00 h and 2.75 h respectively.T1/2 were respectively(14.23±1.9) h and (14.33±1.76) h.AUC0-t were (40 267.24±14 685.17) ng?mL-1?h and (41 167.68±13 947.54) ng?mL-1?h respectively.AUC0-∞ were (41 492.96±15 231.43) ng?mL-1?h and (42 392.65±14 397.83) ng?mL-1?h respectively.The 90% confidential interval (90% CI) of AUC0-t,AUC0-∞ and Cmax of the test and reference preparations were 91.77%~102.20%,91.74%~102.28% and 94.46%~106.53% respectively.The average bioavailability AUC0-t and AUC0-∞ of the test preparation in comparison of the reference were (97.12±1.22) % and (97.15±1.17) % respectively.Conclusion The test imatinib mesylate tablet showed bioequivalence with the reference preparation in oral administration postprandial state.