Zhang Yifan, Chen Xiaoyan, Tang Yunbiao, Lu Youming, Guo Lixia, Zhong Dafang
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai.
Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People's Republic of China.
Drug Des Devel Ther. 2017 Jul 11;11:2109-2119. doi: 10.2147/DDDT.S138286. eCollection 2017.
The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax 70 mg tablet.
A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods.
The average maximum concentrations () of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration-time curves from time 0 to the last timepoint (AUC ) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h⋅ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product ( ) for and AUC were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for and AUC , respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for and AUC were 90.35%-129.04% and 85.31%-117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%-143.19% and 80.00%-125.00%.
The generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting conditions.
本研究旨在评估70毫克阿仑膦酸钠片仿制药与参比制剂福善美70毫克片剂的生物等效性。
在36名健康中国男性志愿者中进行了一项单中心、开放标签、随机、三周期、三序列、参比制剂重复的交叉研究，研究在空腹条件下进行。在每个研究周期，志愿者接受单次口服剂量的仿制药或参比制剂（70毫克）。在给药前及给药后长达8小时采集血样。采用美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的参比标化平均生物等效性（RSABE）方法评估仿制药与参比制剂的生物等效性。
单次服用仿制药以及参比制剂的第一剂和第二剂后，阿仑膦酸的平均最大浓度（）分别为64.78±43.76、56.62±31.95和60.15±37.12纳克/毫升。从时间0到最后一个时间点的血浆浓度-时间曲线下面积（AUC）分别为150.36±82.90、148.15±85.97和167.11±110.87小时·纳克/毫升。使用参比标化是因为参比制剂的个体内标准差（）对于和AUC均高于0.294的临界值。对于和AUC，95%置信区间上限分别为-0.16和-0.17，仿制药/参比制剂比值的点估计值分别为1.08和1.00，满足FDA的RSABE接受标准。对于和AUC，90%置信区间分别为90.35%-129.04%和85.31%-117.15%，在EMA规定的生物等效性69.84%-143.19%和80.
