两种西地那非片在健康人体内的生物等效性  

Bioequivalence of two kinds of sildenafil tablets in healthy volunteers

作　　者：李筱旻[1] 徐素梅[1] 周文智 邹婷[1] 郭洁 徐平声[1] LI Xiao-min;XU Su-mei;ZHOU Wen-zhi;ZOU Ting;GUO Jie;XU Ping-sheng(Phase I Clinical Research Unit,Xiangya Hospital,Central South University,Changsha HU-NAN 410008,China)

机构地区：[1]中南大学湘雅医院Ⅰ期临床试验研究中心

出　　处：《中国新药与临床杂志》2020年第2期102-107,共6页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的研究两种西地那非片在中国健康人体内的生物等效性。方法空腹试验48例、餐后试验40例健康男性志愿者随机交叉单剂量口服西地那非片受试制剂与参比制剂100 mg,采用液相色谱-质谱(LC-MS/MS)法测定血浆中西地那非和N-去甲基西地那非的血药浓度,应用SAS 9.4统计软件进行统计分析,计算药动学参数及相对生物利用度,判定两制剂是否等效。结果空腹试验中受试制剂与参比制剂西地那非的主要药动学参数cmax分别为(566±244)和(550±256)ng·mL^-1,AUC0-t分别为(1388±520)和(1407±545)ng·h·mL^-1,AUC0-∞分别为(1403±520)和(1422±544)ng·h·mL^-1;N-去甲基西地那非的主要药动学参数cmax分别为(291±110)和(280±101)ng·mL^-1,AUC0-t分别为(936±381)和(956±429)ng·h·mL^-1,AUC0-∞分别为(953±387)和(974±435)ng·h·mL^-1。餐后试验中受试制剂与参比制剂西地那非的主要药动学参数cmax分别为(424±137)和(422±145)ng·mL^-1,AUC0-t分别为(1660±505)和(1654±536)ng·h·mL^-1,AUC0-∞分别为(1675±506)和(1667±540)ng·h·mL^-1;N-去甲基西地那非的主要药动学参数cmax分别为(206±66)和(206±74)ng·mL^-1,AUC0-t分别为(930±280)和(954±351)ng·h·mL^-1,AUC0-∞分别为(945±283)和(970±356)ng·h·mL^-1。受试制剂与参比制剂cmax、AUC0-t和AUC0-∞几何均数比值的90%置信区间均完全落在80.00%~125.00%之间。结论本研究建立的LC-MS/MS法准确快速,灵敏度高,专属性强,适用于西地那非及N-去甲基西地那非血药浓度测定。两种西地那非片具有生物等效性。AIM To study the bioequivalence of two kinds of sildenafil tablets in Chinese healthy volunteers.METHODS A randomized crossover study designing was adopted in the study.Forty-eight healthy male volunteers in fasting test and forty healthy male volunteers in fed test were given single oral dose of sildenafil(100 mg).The concentration of sildenafil and N-desmethyl sildenafil in plasma was measured by LC-MS/MS.All statistic analysis were performed by using SAS 9.4 statistics software.Pharmacokinetic parameters and relative bioavailability were calculated to determine whether the two preparations were bioequivalent.RESULTS In fasting test,the pharmacokinetic parameters of sildenafil of the test(T)and reference(R)preparation were as follow:cmax were(566±244)and(550±256)ng·mL^-1,AUC0-t were(1388±520)and(1407±545)ng·h·mL^-1,AUC0-∞ were(1403±520)and(1422±544)ng·h·mL^-1.The pharmacokinetic parameters of N-desmethyl sildenafil of T and R were as follow:cmax were(291±110)and(280±101)ng·mL^-1,AUC0-t were(936±381)and(956±429)ng·h·mL^-1,AUC0-∞ were(953±387)and(974±435)ng·h·mL^-1.In the fed test,the pharmacokinetic parameters of sildenafil of T and R were as follow:cmax were(424±137)and(422±145)ng·mL^-1,AUC0-t were(1660±505)and(1654±536)ng·h·mL^-1,AUC0-∞were(1675±506)and(1667±540)ng·h·mL^-1.The pharmacokinetic parameters of N-desmethyl sildenafil of T and R were as follow:cmax were(206±66)and(206±74)ng·mL^-1,AUC0-t were(930±280)and(954±351)ng·h·mL^-1,AUC0-∞ were(945±283)and(970±356)ng·h·mL^-1.The 90%confidence interval for geometric mean ratio of cmax,AUC0-t and AUC0-∞ were all in the area of 80.00%-125.00%.CONCLUSION The LC-MS/MS method established in this study is accurate,rapid,sensitive,and specific,and is applicable to determine the concentration of sildenafil and N-desmethyl sildenafil.The two kinds of sildenafil tablets were bioequivalent.

关 键 词：西地那非 色谱法 液相 串联质谱法 生物等效性 

分 类 号：R969.1[医药卫生—药理学]