非诺贝特微粉化胶囊在健康志愿者体内的生物等效性

Bioequivalence of micronized fenofibrate capsule in healthy volunteers

目的研究国产和进口非诺贝特微粉化胶囊在健康受试者体内的药动学特征,评估两者生物等效性。方法 20名健康男性志愿者采用2制剂双周期交叉试验设计,以酮洛芬为内标,HPLC法测定血浆中非诺贝特酸的浓度,以BAPP2.2软件计算其药动学参数。结果 20名受试者单剂量口服200 mg参比制剂和受试制剂后,主要药动学参数ρmax分别为(5.3±s 2.1)mg.L-1和(4.4±1.5)mg.L-1;tmax分别为(6.4±2.5)h和(5.8±1.6)h;t1/2分别为(23±5)h和(26±8)h;MRT为(35±8)h和(38±11)h;AUC0～72为(127±35)mg.h.L-1和(118±28)mg.h.L-1;AUC0～∞为(145±41)mg.h.L-1和(140±34)mg.h.L-1。主要药动学参数经统计学分析,无显著差异(P>0.05)。2种制剂的相对生物利用度为(97±29)%。结论 2种制剂具有生物等效性。

AIM To evaluate the bioequivalence of meclofenoxate dispersible tablets and capsules in Chinese healthy volunteers.METHODS The study was performed in 18 healthy male volunteers according to a randomized 2-way crossover design.The blood samples were collected at 0 h and 0.33,0.67,1,1.5,2,2.5,3,4,6,8,10,14,24 h after taking 200 mg of meclofenoxate dispersible tablets（test drug）and meclofenoxate capsules（reference drug）,and with repeated sampling of the crossover drug administration 7 d after clearance.The concentration of chlorophenoxyacetic acid in plasma was determined by HPLC.The pharmacokinetic parameters were calculated and compared statistically to evaluate the relative bioequivalence between the two preparations of meclofenoxate by DAS Ver2.0 software.RESULTS The major pharmacokinetic parameters of meclofenoxate dispersible tablets and meclofenoxate capsules were as follows：tmax were（1.8 ± s 0.3）and（2.1 ± 0.3）h,ρmax were（13.9 ± 2.6）and（12.8 ± 2.8）mg·L-1,t1/2 were（6.1 ± 2.0）and（6.0 ± 2.1）h,AUC0-t were（36 ± 9）and（34 ± 8）mg·h·L-1,AUC0-∞ were（36 ± 9）and（35 ± 8）mg·h·L-1,respectively.The relative bioavailability of test drug was（105 ± 10）%.CONCLUSION Meclofenoxate dispersible tablets and meclofenoxate capsules are bioequivalent in Chinese healthy volunteers.