阿德福韦酯片在中国健康受试者中的药代动力学和生物等效性研究

Study on pharmacokinetics and bioequivalence adefovir dipivoxil tablets in Chinese healthy subjects

目的研究阿德福韦酯片受试制剂(10mg)和参比制剂(10 mg)在健康人空腹及餐后状态下的药代动力学特征,并对两种制剂的生物等效性进行评价。方法空腹试验24例健康受试者,餐后试验26例健康受试者,按双周期、自身交叉设计、单剂量口服阿德福韦酯片受试制剂或参比制剂10 mg,使用高效液相色谱-串联质谱(HPLC-MS/MS)法测定给药后不同时间点的血药浓度,采用Phoenix WinNonlin软件(7.0版本)进行非房室模型药代动力学参数的估算分析,评价两种制剂的生物等效性。结果单次空腹口服药物后,参比制剂和受试制剂的C_(max)分别为(24.92±6.01)和(24.04±3.58)ng·mL^(-1),AUC_(0-t)为(284.85±45.04)和(299.69±49.31)ng·h·mL^(-1),AUC_(0-∞)为(304.44±47.58)和(317.27±50.04)ng·h·mL^(-1),t_(max)为0.75和1 h,t1/2为(9.02±1.06)和(9.60±1.81)h。在餐后试验中,参比制剂和受试制剂的C_(max)分别为(22.88±4.09)和(22.88±4.19)ng·mL^(-1),AUC_(0-t)为(287.42±52.07)和(291.11±53.68)ng·h·mL^(-1),AUC_(0-∞)为(302.74±52.95)和(308.05±53.88)ng·h·mL^(-1),t_(max)为3.5和3.5 h,t1/2为(9.54±2.47)和(9.17±2.03)h。受试制剂与参比制剂几何均值比的90%置信区间均完全落在80.00%~125.00%。结论2种阿德福韦酯片在中国健康受试者体内具有生物等效性。

Objective To study the pharmacokinetic characteristics of adefovir dipivoxil tablets(10 mg)and reference preparation(10 mg)in healthy people in fasting and postprandial states,and evaluate the bioequivalence of the two preparations.Methods Twenty-four healthy subjects in the fasting test and twenty-six healthy subjects in the fed test were given a single dose of 10 mg of the test or reference preparation of adefovir dipivoxil tablets according to a two-period,self-crossover design.The plasma concentrations at different time points after administration were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The pharmacokinetic parameters of the non-compartment model were estimated and analyzed by Phoenix WinNonlin software(version 7.0)to evaluate the bioequivalence of the two preparations.Results After a single fasting oral administration,the C_(max) of the reference and test pre pa rations were(24.92±6.01)and(24.04±3.58)ng·mL^(-1),AUC_(0-t) were(284.85±45.04)and(299.69±49.31)ng·h·mL^(-1),AUC_(0-∞)were(304.44±47.58)and(317.27±50.04)ng·h·mL^(-1),tmax were 0.75 and 1 h,t1/2 were(9.02±1.06)and(9.60±1.81)h.In the postprandial test,the C_(max) of the reference and test preparation were(22.88±4.09)and(22.88±4.19)ng·mL^(-1),AUC_(0-t) were(287.42±52.07)and(291.11±53.68)ng·h·mL^(-1),AUC_(0-∞)were(302.74±52.95)and(308.05±53.88)ng·h·mL^(-1),tmax were 3.5 and 3.5 h,t1/2 were(9.54±2.47)and(9.17±2.03)h.The 90%confidence interval of the geometric mean ratio of the test preparation to the reference preparation fell completely between 80.00%and 125.00%.Conclusion Two adefovir dipivoxil tablets were bioequivalent in healthy Chinese subjects.