Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax (R) tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

doi:10.2147/DDDT.S138286

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	Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax (R) tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study
	Zhang, Yifan1 ; Chen, Xiaoyan1 ; Tang, Yunbiao 2; Lu, Youming 1; Guo, Lixia 1; Zhong, Dafang1
刊名	DRUG DESIGN DEVELOPMENT AND THERAPY
	2017
卷号	11 页码:2109-2119
关键词	alendronate sodium pharmacokinetics highly variable drug reference-scaled average bioequivalence
ISSN号	1177-8881
DOI	10.2147/DDDT.S138286
文献子类	Article
英文摘要	Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax (R) 70 mg tablet. Materials and methods: 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. Results: The average maximum concentrations (C-max) 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(0-t)) 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 (s(WR)) for C-max and AUC(0-t) were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for C-max and AUC(0-t), 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 C-max and AUC(0-t) 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%. Conclusion: 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.
WOS关键词	HIGHLY VARIABLE DRUGS ; SCALED AVERAGE BIOEQUIVALENCE ; PHARMACOKINETICS ; BIOAVAILABILITY ; BISPHOSPHONATES ; OSTEOPOROSIS ; FORMULATIONS ; WOMEN ; FDA
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	DOVE MEDICAL PRESS LTD
WOS记录号	WOS:000405618500002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275706]
专题	上海药物代谢研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zhong, Dafang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201210, Peoples R China; 2.Gen Hosp Shenyang Mil Reg, Dept Pharm, Shenyang, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Yifan,Chen, Xiaoyan,Tang, Yunbiao,et al. Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax (R) tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2017,11:2109-2119.
APA	Zhang, Yifan,Chen, Xiaoyan,Tang, Yunbiao,Lu, Youming,Guo, Lixia,&Zhong, Dafang.(2017).Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax (R) tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study.DRUG DESIGN DEVELOPMENT AND THERAPY,11,2109-2119.
MLA	Zhang, Yifan,et al."Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax (R) tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study".DRUG DESIGN DEVELOPMENT AND THERAPY 11(2017):2109-2119.