吗替麦考酚酯胶囊人体生物等效性研究

目的:研究吗替麦考酚酯胶囊在健康人体内的生物等效性。方法:24名受试者单剂量、交叉口服吗替麦考酚酯胶囊受试制剂或参比制剂1000mg后,采用高效液相色谱法,二极管阵列检测器和荧光检测器串联检测霉酚酸(MPA)及霉酚酸葡糖醛酸酯(MPAG)的血药浓度,以DAS2.0.1程序计算药动学参数和生物等效性数据。结果:受试制剂与参比制剂的MPA,其Cmax分别为(45.728±16.006)、(49.323±16.098)μg·mL-1,tmax分别为(0.610±0.242)、(0.534±0.260)h,t1/2分别为(14.214±6.308)、(12.707±6.575)h,AUC0～60分别为(84.697±19.917)、(84.312±18.639)μg.h.mL-1,AUC0～∞分别为(89.750±20.728)、(102.995±68.151)μg.h.mL-1;受试制剂与参比制剂的MPAG,其Cmax分别为(54.917±14.715)、(53.916±10.703)μg.mL-1,tmax分别为(1.521±0.454)、(1.396±0.294)h,t1/2分别为(13.542±6.685)、(11.885±3.130)h,AUC0～60分别为(486.686±145.059)、(446.812±100.383)μg.h.mL-1,AUC0～∞分别为(524.357±127.385)、(471.725±101.297)μg.h.mL-1;MPA的相对生物利度为(100.39±16.9)%,MPAG的相对生物利度为(106.89±18.6)%。结论:吗替麦考酚酯胶囊受试制剂与参比制剂具有生物等效性。

Bioequivalence of Mycophenolate Mofetil Capsules in Health Volunteers

OBJECTIVE： To investigate the bioequivalence of mycophenolate mofetil capsules in health volunteers. METHODS： A single oral dose of test and reference formulations （1 000 mg） were given to 24 health volunteers in a randomized crossover study. The concentrations of myeophenolic acid and its glucuronide in plasma were determined by HPLC using series connection of diode array detector and fluorescence detector. The pharmacokinetic parameters were calculated and the bioequivalence of two formulations were evaluated by Drug and Statistics Program （DAS2.0.1） . RESULTS： The pharmacokinetic parametersfor the test and reference formulations of mycophenolie acid were as follows： Cmax were （45.728 ±16.006） and （49.323±16.098） μg·mL^-1; tmax were （0.610±0.242） and （0.534±0.260）h; t1/2 were （14.214±6.308） and （12.707± 6.575） h; AUC0-60 were （84.697±19.917） and （84.312± 18.639） μg·h·mL^-1; AUC0-∞ were （89.750± 20.728） and （102.995± 568.151）μg·h·mL^-1 respectively. The pharmacokinetic parameters for the test and reference formulations of Mycophenolic acid glucuronide were as follows： Cmax were （54.917± 14.715） and （53.916± 10.703） μg·h·mL^-1; tmax were （1.521±0.454） and （1.396±0.294） h; t1/2 were （13.542±6.685） and （11.885±3.130） h; AUC0-60 were （486.686± 145.059） and （446.812± 100.383） μg·h·mL^-1; AUC0-∞ were （524.357± 127.385） and （471.725± 101.297）μg·h·mL^-1 respectively. The relative bioavailability of mycophenolic acid was （100.39 ± 16.9） % and that of mycophenolic acid glucuronide was （106.89± 18.6） %. CONCLUSION： The test and reference capsules of mycophenolate capsules were bioequivalent.