吗替麦考酚酯干混悬剂的人体药动学及生物等效性研究

目的:研究国产吗替麦考酚酯(MMF)干混悬剂和进口片剂在健康人体的药动学及生物等效性。方法:采用随机自身对照双周期交叉试验设计,20名健康男性志愿者口服MMF干混悬剂或进口片剂0.75mg,用高效液相色谱法测定MMF的活性代谢产物麦考酚酸(MPA)的血药浓度,用非房室模型法计算MPA的药动学参数,用方差分析和双单侧t检验评价2种制剂的生物等效性。结果:MMF干混悬剂和进口片剂的药动学参数:t1/2β分别为(16.80±4.10)、(16.77±4.50)h,tmax分别为(0.4±0.1)、(0.7±0.4)h,Cmax分别为(19.29±6.78)、(18.22±7.19)μg.mL-1,AUC0～72分别为(39.22±10.43)、(39.38±10.46)μg.h.mL-1,AUC0～∞分别为(40.58±10.49)、(41.00±10.88)μg.h.mL-1。受试制剂的相对生物利用度为(100.9±10.6)%。结论:2种MMF制剂在人体内生物等效。

Pharmacokinetics and Bioequivalence of Mycophenolate Mofetil Dry Suspension in Healthy Volunteers

OBJECTIVE： To study the pharmacokinetics and the bioequivalence of mycophenolate mofetil （MMF） dry suspension versus its imported tablets counterpart in healthy volunteers. METHODS： In a randomized two period crossover study, each of the 20 healthy male volunteers received a single oral dose of 0.75 mg dry suspension or imported tablet of MMF.The plasma concentration of mycophenolic acid （MPA）, which is the active metabolite of MMF, were determined by HPLC. The pharmacokinetics of MPA were estimated by the non - compartment model and the bioequivalence of the two formulations of MMF were evaluated by ANOVA and two one - sided - test. RESULTS： The main pharmacokinetic parameters of MMF dry suspension versus imported MMF tablet were as follows ： t 1/2β were （ 16.80 _± 4.10） and （ 16.77± 4.50） h ; t max were （0.4± 0.1） and （0.7 ± 0.4） h ; Cmax were （ 19.29 ± 6.78） and （ 18.22 ± 7.19）μg·mL^-1 AUC0-72 were （39.22 ± 10.43） and （39.38 ± 10.46）μg·mL^-1, and AUC0-∞ were （40.58± 10.49） and （41.00± 10.88） μg·mL^-1 respectively. The relative bioavailability of the test preparation （dry suspension of MMF） was （ 100.9± 10.6） %. CONCLUSION ： The two formulations are bioequivalent in healthy volunteers.