甲磺酸伊马替尼片在中国健康受试者中的餐后生物等效性研究

Bioequivalence Study of Imatinib Mesylate Tablets in Post-prandial Conditions in Healthy Chinese Volunteers

目的建立测定人体血浆中伊马替尼的超高效液相色谱-串联质谱(UPLC-MS/MS)。并评价甲磺酸伊马替尼片的相对生物利用度和生物等效性。方法24例健康受试者随机分为2组,分别餐后口服甲磺酸伊马替尼片受试或参比制剂400 mg,采用UPLC-MS/MS测定人血浆伊马替尼浓度。采用WinNonlin 6.4版统计软件计算药代动力学参数,SAS 9.2版软件评价两制剂的生物等效性。结果受试者餐后口服受试或参比制剂后,血浆中伊马替尼分别在3.47(1.98~5.98)和2.97(1.98~6.00)h达到峰浓度(2308.3±873.59)和(2119.6±597.20)ng·mL^-1;t1/2分别为(14.23±1.45)和(14.01±1.99)h;AUC0-t分别为(39724.7±18670.30)和(35294.4±7991.97)h·ng·mL^-1;AUC0-inf分别为(40111.0±19014.95)和(35595.0±8048.28)h·ng·mL^-1。两种制剂的Cmax、AUC0-t和AUC0-inf经对数转换后90%可信区间分别为95.52%~119.59%、97.07%~119.35%和97.10%~119.39%。结论甲磺酸伊马替尼片受试与参比制剂在餐后条件下具有生物等效性。

Objective To establish an ultra-high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for the determination of imatinib in human plasma,and to evaluate the relative bioavailability and bioequivalence of imatinib mesylate tablets in post-prandial conditions in Chinese healthy volunteers.Methods Twenty four healthy volunteers were randomly divided into two groups.Each group received a single oral dose of 400 mg imatinib mesylate tablet as a test or reference drug in post-prandial conditions.UPLC-MS/MS was used to determine the concentration of imatinib in plasma.The pharmacokinetic parameters were calculated by the WinNonlin 6.4 statistical software,and the bioequivalence of the two preparations was evaluated by the SAS 9.2 software.Results After oral administration of test or reference preparation,imatinib in plasma reached peak concentration(2308.3±873.59)and(2119.6±597.20)ng·mL^-1 at 3.47(1.98-5.98)h and 2.97(1.98-6.00)h,respectively.AUC0-t were(39724.7±18670.30)and(35294.4±7991.97)h·ng·mL^-1;AUC0-inf were(40111.0±19014.95)and(35595.0±8048.28)h·ng·mL^-1.The 90%confidence intervals of Cmax,AUC0-t and AUC0-inf for two preparations after a logarithmic transformation were 95.52%-119.59%,97.07%-119.35%,and 97.10%-119.39%,respectively,which were all within the limits of 80.00%-125.00%.Conclusion It could therefore be concluded that the test preparation of imatinib mesylate tablets was bioequivalent to that of Gleevec tablets(reference).