麦考酚酸酯分散片在健康人体的药动学和生物等效性

目的:研究麦考酚酸酯(MMF)国产分散片和进口胶囊在健康人体的药动学及其生物等效性。方法:采用随机自身对照双周期交叉试验设计,18名男性健康志愿者口服MMF分散片或胶囊各1．0 g,用反相高效液相色谱一紫外检测法测定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分散片与胶囊麦考酚酸的药动学参数如下:t_(max)分别为(0．62±s 0．21),(0．74±0．23)h;c_(max)分别为(27±5), (28±6)mg·L~(-1);AUC0～36分别为(51±9),(49±9)mg·h·L~(-1);t1/2分别为(13．7±2．5),(13．9±2．5)h。国产麦考酚酸酯分散片中麦考酚酸相对于胶囊的相对生物利用度为(104±9)％,2种制剂的主要药动学参数经统计学检验,两者差异无显著意义(P＞0．05)。结论:2种制剂在人体内生物等效。

Pharmacokinetics and bioequivalence of mycophenolate mofetil dispersible tablets in healthy volunteers

AIM:To evaluate the pharmacokinetics and bioequivalence of myeophenolate mofetil(MMF) dispersible tablets and capsules(Cellcept)in healthy volunteers.METHODS:In a randomized two-period crossover study,18 healthy volunteers received a single oral dose of 1.0 g MMF dispersible tablet or capsule in- dividually.The plasma concentrations of mycophenolic acid(MPA),the active metabolite of MMF,were deter- mined by RP-HPLC-UV.The parameters of pharmacokinetic of MPA were estimated by the non-compartment model.The bioequivalence of the two preparations were evaluated with a statistic analysis of ANOVA and two one-sided t test.RESULTS:The pharmacokinetic parameters of MMF dispersible tablets and capsules were t_(max) (0.62±s0.21),(0.74±0.23)h;c_(max)(27±5),(28±6)mg·L~(-1);AUC_(0～36)(51±9),(49±9)mg·h·L~(-1); and t_(1/2)(13.7±2.5),(13.9±2.5)h,respectively.The relative bioavailability of MPA in MMF tablet to that of the capsule was(104±9)% showing no significant difference between the test and reference preparations statistically(P＞0.05).CONCLUSION:The two formulations of MMF tablets and capsules are bioequivalent in human.