目的建立非诺贝特酸简单快速的血浆样品提取方法,比较研究2种进口非诺贝特的人体相对生物利用度。方法血浆样品加内标地西泮和乙腈,涡旋振荡,高速离心,上清液进样分析。采用两制剂二周期自身交叉试验方法,18名健康志愿者分别口服非诺贝特胶囊受试制剂和参比制剂各200mg,HPLC测定血浆非诺贝特酸浓度,DAS软件计算药动学和相对生物利用度。结果非诺贝特在人体内代谢为非诺贝特酸,非诺贝特酸和内标地西泮分离良好,二者的t_R分别4.10和5.40min左右。非诺贝特胶囊受试制剂和参比制剂的峰浓度ρ_max分别为(9.04±1.65)和(9.51±1.77)mg·L^-1;达峰时间t_max分别为(4.61±1.04)和(5.0±0.77)h;半衰期t_1/2分别为(19.75±6.17)和(18.98±5.40)h;血药浓度-时间曲线下面积AUC_0-t分别为(151.96±41.76)和(160.59±50.07)mg·h·L^-1;受试制剂的相对生物利用度F_0-t为(97.5±22.6)%。结论非诺贝特胶囊受试制剂和参比制剂生物等效。

OBJECTIVE To establish a simple extract method for the analysis and quantitative determination of fenofibric acid in plasma,and compare relative bioavailability of fenofibrate test preparations with reference preparations in healthy volunteers.METHODS Blood sample with diazepam was deproteinized by acetonitrile.A total of 18 healthy male volunteers were administered with two preparations of fenofibrate in a randomized crossover design.Fenofibric acid was determined by HPLC after a single oral administration of 200 mg in healthy volunteers.The pharmacokinetic parameters and relative bioavailability of fenofibric acid were obtained using DAS software.RESULTS Fenofibric acid,the active circulating metabolite of fenofibrate,was obtained from blood sample.The retention times(t_R)of fenofibric acid and diazepam were about 4.10 and 5.40 min,respectively.The pharmacokinetic parameters of fenofibric acid for test preparations(T)and reference preparations(R)were as following:ρ_max were(9.04±1.65)and(9.51±1.77)mg·L^-1,t_max were(4.61±1.04)and(5.0±0.77)h,t_1/2 were(19.75±6.17)and(18.98±5.40)h,AUC_0-t were(151.96±41.76)and(160.59±50.07)mg·h·L^-1,respectively.The relative bioavailability of test preparations(F_0-t)was calculated to be(97.5±22.6)%,compared with reference preparations.CONCLUSION The two preparations of fenofibrate are bioequivalent.