两种阿德福韦酯在健康人体内的生物等效性  

Bioequivalence of two kinds of adefovir dipivoxil in healthy volunteers

作　　者：李相鸿[1] 孙华[1] 周理想[1] 梁大虎[1] 杨斌[1] 王伟佳[1] 戴敏[1] 赵亚男[1] 沈杰[1] 谢海棠[1] LI Xiang-hong;SUN Hua;ZHOU Li-xiang;LIANG Da-hu;YANG Bin;WANG Wei-jia;DAI Min;ZHAOYa-nan;SHEN Jie;XIE Hai-tang(Drug Clinical Trial Institution/Anhui Prorincial Center for Drug Clinical Eoaluation,Yijishan Hospital of Warnan MedicalCollege,Wuhu ANHUI 241000,China)

机构地区：[1]皖南医学院弋矶山医院―药物临床试验机构/安徽省药物临床评价中心,安徽芜湖241000

出　　处：《中国新药与临床杂志》2021年第5期379-383,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的研究阿德福韦酯分散片在中国健康人体内的生物等效性。方法36名健康志愿者分别在空腹和餐后条件下随机两周期两交叉口服受试制剂10 mg和参比制剂10 mg,采用高效液相色谱-串联质谱(HPLC-MS/MS)法测定给药后不同时间点血浆中阿德福韦浓度,采用Phoenix Winnonlin 8.0计算药动学参数并考察两制剂生物等效性。结果空腹试验中受试制剂和参比制剂的主要药动学参数cmax分别为(22.9±4.9)、(21.2±4.3)μg·L-1,AUC0-36h分别为(250.7±56.1)、(250.5±54.7)μg·h·L^(-1)AUC0-∞分别为(265.6±57.8)、(265.1±56.8)μg·h·L^(-1)tmax分别为(1.5±1.2)、(1.2±0.6)h,t1/2分别为(7.2±1.3)、(7.4±1.4)h;餐后试验中受试制剂和参比制剂的主要药动学参数cmax分别为(15.9±3.2)、(15.8±3.6)μg·L-1,AUC0-36h分别为(194.8±40.8)、(189.4±44.9)μg·h·L^(-1)AUC0-∞分别为(208.6±43.1)、(204.1±46.6)μg·h·L^(-1)tmax分别为(3.7±1.1)、(4.0±1.2)h,t1/2分别为(8.1±1.7)、(7.8±1.5)h。结论建立的HPLC-MS/MS分析方法准确、灵敏,两种制剂在空腹和餐后给药情况下均生物等效,高脂饮食会对部分药动学参数产生一定影响。AIM To study the bioequivalence of adefovir dipivoxil dispersible tablets in Chinese healthy volunteers.METHODS Thirty-six healthy volunteers were randomly divided into two groups for two periods and two crosses oral administration of test formulation(T)and reference formulation(R)of 10 mg under fasting and fed conditions,respectively.Plasma concentration of adefovir at different time points after administration was determined by HPLC-MS/MS method.Pharmacokinetic parameters were calculated by Phoenix Winnonlin 8.0 to study its bioequivalence.RESULTS The main pharmacokinetic parameters of test formulation and reference formulation under fasting condition were as follows:cmax(22.9±4.9)and(21.2±4.3)μg·L-1,AUC0-36h(250.7±56.1)and(250.5±54.7)μg·h·L^(-1)AUC0-∞(265.6±57.8)and(265.1±56.8)μg·h·L^(-1)tmax(1.5±1.2)and(1.2±0.6)h,t1/2(7.2±1.3)and(7.4±1.4)h,respectively.The main pharmacokinetic parameters of test formulation and reference formulation under fed condition were as follows:cmax(15.9±3.2)and(15.8±3.6)μg·L-1,AUC0-36h(194.8±40.8)and(189.4±44.9)μg·h·L^(-1)AUC0-∞(208.6±43.1)and(204.1±46.6)μg·h·L^(-1)tmax(3.7±1.1)and(4.0±1.2)h,t1/2(8.1±1.7)and(7.8±1.5)h,respectively.CONCLUSION The HPLC-MS/MS analysis method is accurate and sensitive.Test formulation and reference formulation of adefovir are bioequivalent under fasting and fed conditions.Diet may have an effect on some pharmacokinetic parameters.

关 键 词：阿德福韦 色谱法 高压液相 串联质谱法 生物等效性 

分 类 号：R969.1[医药卫生—药理学]