国产与进口非诺贝特胶囊人体生物等效性研究

Bioequivalence of Domestic and Imported Fenofibrate Capsules in Healthy Volunteers

目的:研究国产与进口非诺贝特胶囊的人体生物等效性。方法:18名健康受试者采用双周期自身交叉试验,单剂量口服国产(受试制剂)与进口(参比制剂)非诺贝特胶囊200mg,以高效液相色谱法测定血浆中非诺贝酸的浓度,药-时数据经BECS生物利用度和等效性统计软件处理,计算主要药动学参数,并评价二者的生物等效性。结果:国产与进口非诺贝特胶囊的主要药动学参数分别为:t1/(221.34±3.31)、(21.83±4.35)h,Cma(x7.31±2.65)、(7.28±2.66)mg·L-1,tma(x4.72±0.57)、(4.67±0.59)h,AUC0～7(2170.09±54.06)、(172.2±54.64)mg·h·L-1,AUC0～∞(188.56±55.27)、(192.27±56.62)mg·h·L-1。国产非诺贝特胶囊的相对生物利用度F0～72为(98.87±6.76)%,F0～∞为(98.00±6.72)%。tmax采用非参数检验,Cmax、AUC0～72经对数转换后用方差分析和双单侧t检验,2种制剂的结果差异均无统计学意义。受试制剂AUC0～72和Cmax的90%可信限分别落在参比制剂的83.3%～116.9%和81.1%～124.4%范围内。结论:2种制剂生物等效。

OBJECTIVE： To evaluate the bioequivalence of domestic and imported Fenofibrate capsules in healthy volunteers. METHODS： In double-period crossover study, 18 healthy volunteers received a single oral dose of domestic Fenofibrate capsule 200 mg （test capsule） and imported capsule 200 mg （reference capsule）. The content of fenofibric acid in plasma was measured with HPLC. BECS pharmacokinetics program was used to calculate the pharmacokinetic parameters and bioavailability and to evaluate the bioequivalence of two preparations. RESULTS： The main pharmacokinetic parameters of domestic Fenofibrate capsule vs. imported Fenofibrate capsule were as follows： t1/2（21.34±3.31） h vs.（21.83±4.35） h, Cmax（7.31±2.65） mg·L^-1 vs. （7.28±2.66） mg·L^-1, tmax（4.72±0.57） h vs.（4.67±0.59） h, AUC0～72（170.09±54.06） mg·h·L^-1 vs. （172.2±54.64） mg·h·L^-1, AUC0～∞（188.56±55.27） mg·h·L^-1 vs. （192.27±56.62） mg·h·L^-1. The relative bioavailability F0～72 and F0～∞ of domestic Fenofibrate capsule were（98.87±6.76）% vs.（98.00±6.72）%, respectively. Non-parameter test of tmax and variance analysis and t-test of Cmax and AUC0～72 showed there was no statistical difference between 2 kinds of Fenofibrate capsules. The 90% confidential intervals of AUC0～72 and Cmax of test capsule were 83.3%～116.9% and 81.1%～124.4%, respectively. CONCLUSION： The domestic and imported Fenofibrate capsules are bioequivalent.