吗替麦考酚酯胶囊人体生物等效性研究

 目的建立HPLC-MS/MS测定人血清中霉酚酸(MPA)的浓度,研究MPA的人体药动学过程及吗替麦考酚酯(MMF)胶囊的生物等效性。方法18名健康志愿者按2×2交叉试验方案设计,分别单剂量poMMF胶囊的参比制剂或受试制剂1 000 mg,HPLC-MS/MS测定MPA的血药浓度。以非房室模型计算药动学参数,通过多因素方差分析、双单侧t检验判断2种制剂的生物等效性。结果参比制剂及受试制剂中MPA的主要药动学数据t_max分别为(0.76±0.25)和(0.73±0.27)h,ρ_max分别为(33.10±9.60)和(33.58±11.93)mg·L^-1,AUC_0→t分别为(86.46±16.16)和(83.19±17.18)mg·h·L^-1,AUC_0-inf分别为(89.55±16.84)和(86.52±18.28)mg·h·L^-1,t_1/2分别为(16.52±4.10)和(16.89±4.95)h,k_e分别为(0.044 2±0.009 8)和(0.044 12±0.011 5)h^-1,MRT_0→t分别为(13.15±2.46)和(12.52±2.47)h,VRT_0→t分别为(253.13±57.35)和(245.97±69.57)。受试制剂相对于参比制剂的生物利用度F为(96.32±9.88)%,统计学分析表明,2种制剂生物等效。结论该方法准确、灵敏,无杂质干扰。受试制剂与参比制剂具有生物等效性。

Bioequivalence of Mycophemolate Mofetil Capsule in Healthy Human

OBJECTIVE To establish a HPLC-MS/MS method for the determination of MPA in human serum and application in bioequiavailability study of MMF capsule in heathy volunteers.METHODS 18 Healthy volunteers were envolued in a two period crossover trial.The subjects were administered a single dose of 1 000 mg reference or test MMF capsules,respectively.The serum concentrations of MPA were determined by HPLC-MS/MS.The pharmacokinetic parameters were calculated by noncompartmental analysis.The bioequivalence of the two formulations was evaluated by analysis of variance and two one-sided t test.RESULTS The main pharmacokinetic parameters of reference and test formulations were as follows: t_max(0.76±0.25)and(0.73±0.27)h,ρ_max(33.10±9.60) and(33.58±11.93) mg·L^-1,AUC_{0→72 h}(86.46±16.16) and(83.19±17.18) mg·h·L^-1,AUC_0-inf(89.55±16.84) and(86.52±18.28) mg·h·L^-1,t_1/2(16.52±4.10) and(16.89±4.95)h,k_e(0.044 2±0.009 8) and(0.044 12±0.011 5)h^-1,MRT_{0→72 h}(13.15±2.46) and(12.52±2.47)h,VRT_0→t(253.13±57.35)and(245.97±69.57),respectively.Compared with the reference capsules,the relative bioavailability of test capsule was(96.32 ±9.88) %.The statistical analysis showed that the two formulations were bioequivalent.CONCLUSION The method is accurate and sensitive with no endogenous interference.The two formulations are bioequivalent.