非那雄胺片在中国健康男性受试者空腹和餐后给药的人体生物等效性研究  

Bioequivalence study of finasteride tablets in healthy Chinese male volunteers under fasting and fed conditions

作　　者：胡超[1] 秦永平[1] 舒世清[1] 王颖[1] 朱晓红[1] 罗柱[1] HU Chao;QIN Yong-ping;SHU Shi-qing;WANG Ying;ZHU Xiao-hong;LUO Zhu(Institute of Drug Clinical Trial.GCP Center,Department of Clinical Pharmacology,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院国家药物临床试验机构GCP中心,成都610041

出　　处：《中国新药杂志》2019年第10期1221-1225,共5页Chinese Journal of New Drugs

摘　　要：目的:研究非那雄胺片在中国健康男性人体内的药动学特征,并评价2种非那雄胺片的生物等效性。方法:24例健康男性受试者先后在空腹和餐后状态下随机交叉单剂量口服非那雄胺片受试制剂5 mg与参比制剂5 mg,采用超高效液相色谱串联质谱法(ultra high performance liquid chromatography-mass spectrometry,UPLC-MS/MS)测定不同时点血浆中非那雄胺的浓度,使用WinNonlin 7.0软件进行药动学参数计算,使用SAS 9.4软件进行生物等效性评价。结果:受试者空腹口服试验制剂与参比制剂后,血浆中非那雄胺分别在1.52(0.75～3)和1.75(0.75～4)h达到峰浓度(51.44±12.87)和(47.91±13.70)ng·mL^(-1);AUC_(0-t)分别为(342.58±98.34)和(337.73±87.89)h·ng·mL^(-1);AUC_(0-∞)分别为(348.98±99.92)和(346.65±91.87)h·ng·mL^(-1);t_(1/2)分别为(5.03±1.14)和(5.26±1.00)h。受试者餐后口服试验制剂与参比制剂后,血浆中非那雄胺分别在2.00(1～5)和2.00(0.75～4)h达到峰浓度(54.16±10.54)和(53.12±13.89)ng·mL^(-1);AUC_(0-t)分别为(363.44±95.83)和(360.30±98.48)h·ng·mL^(-1);AUC_(0-∞)分别为(372.37±96.62)和(367.89±98.34)h·ng·mL^(-1);t_(1/2)分别为(5.30±1.32)和(5.25±1.19)h。2种给药条件下,非那雄胺C_(max),AUC_(0-t)和AUC_(0-∞)的几何均值比率(受试制剂/参比制剂)的90%置信区间均在80.00%～125.00%范围内。结论:非那雄胺片受试制剂与参比制剂在空腹和餐后条件下均具有生物等效性。Objective:To evaluate the pharmacokinetics and bioequivalence of two kinds finasteride tablets in Chinese healthy male volunteers.Methods:24 healthy male volunteers were randomised to receive a single oral dose of 5 mg reference or test finasteride tablet under fasting and fed conditions,respectively.UPLC-MS/MS method was used to determine the concentrations of finasteride in plasma.Win Nolin 7.0 and SAS 9.4 software were used for PK parameters calculation and bioequivalence analysis,respectively.Results:The parameters of finasteride test and reference preparations under fasting condition were as follows:Tmaxwere 1.52(0.75~3)h and 1.75(0.75~4)h;Cmaxwere(51.44±12.87)and(47.91±13.70)ng·mL^-1;AUC0-twere(342.58±98.34)and(337.73±87.89)h·ng·mL^-1;AUC0-∞were(348.98±99.92)and(346.65±91.87)h·ng·mL^-1;t1/2 were(5.03±1.14)and(5.26±1.00)h.And under fed condition:Tmaxwere 2.00(1~5)h and 2.00(0.75~4)h;Cmaxwere(54.16±10.54)and(53.12±13.89)ng·mL^-1;AUC0-twere(363.44±95.83)and(360.30±98.48)h·ng·mL^-1;AUC10-∞were(372.37±96.62)and(367.89±98.34)h·ng·mL^-1;t1/2 were(5.30±1.32)and(5.25±1.19)h.The 90%confidence intervals for the rations of Cmax,AUC0-tand AUC0-∞were within the limits of 80.00%~125.00%under those two conditions.Conclusion:Finasteride 5 mg test tablet preparations is bioequivalent to the 5 mg reference preparation under fasting and fed conditions.

关 键 词：非那雄胺 超高效液相色谱串联质谱法 药动学 生物等效性 

分 类 号：R969[医药卫生—药理学]