摘要
目的 以药效学参数血糖的变化为指标,评价中国健康人群阿卡波糖片的生物等效性。方法 根据FDA发布的阿卡波糖生物等效性评价指南,采用随机、开放、双周期交叉试验设计,32名中国健康受试者单剂量交叉口服受试或参比制剂50 mg,测定受试者仅服蔗糖和次日药糖同服后血清葡萄糖浓度。以只服蔗糖血清葡萄糖为基线,计算药糖同服后血清葡萄糖的降低值。采用FDA推荐的Δcmax,AUEC0-4 h进行生物等效性评价,并增加评价指标AUEC0-2 h,AUEC0-1.5 h,AUEC0-1.0 h和ΔGE。结果 服用受试和参比制剂后,血清葡萄糖的Δcmax为(1.169±0.719)和(0.878±0.571) mmol·L-1,AUEC0-2 h为(46±25)和(50±21) mmol·min·L-1,AUEC0-1.5 h为(62±42)和(70±29) mmol·min·L-1,AUEC0-1 h为(59±52)和(73±32) mmol·min·L-1,ΔGE为(1.829±0.952)和(1.656±0.764) mmol·L-1,AUEC0-4 h出现负值,此参数无法用于评估。结论 受试与参比制剂不等效。这可能与阿卡波糖剂量有关,50 mg剂量偏小,也有可能评价参数仍需优化。
Abstract
OBJECTIVE To evaluate the bioequivalence of acarbose tablet in healthy Chinese volunteers through the use of pharmacodynamics endpoint parameters of serum glucose. METHODS Following the Food and Drug Administration (FDA) guidance, a single oral dose of test and reference formulations was given to 32 healthy Chinese volunteers according to a randomized crossover design. Serum glucose concentrations after sucrose administration and co-administration of sucrose and acarbose on the following day were both determined. The reduction of serum glucose concentration were calculated following treatment with acarbose and sucrose together relative to the baseline serum glucose concentration observed . The parameters of Δcmax and AUEC0-4 h recommended by the FDA were used for bioequivalence evaluation. Four pharmacodynamics parameters of AUEC0-2 h,AUEC0-1.5 h, AUEC0-1.0 hand ΔGE were also tested in the evaluation. RESULTS The main pharmacodynamics parameters of serum glucose in test and reference formulations were as follows:Δcmax (1.169±0.719) and (0.878±0.571) mmol·L-1, AUEC0-2 h(46±25) and (50±21) mmol·min·L-1, AUEC0-1.5 h(62±42) and (70±29) mmol·min·L-1, AUEC0-1 h(59±52) and (73±32) mmol·min·L-1, ΔGE(1.829±0.952) and (1.656±0.764) mmol·L-1, respectively. The parameter AUEC0-4 h could not be evaluated due to the presence of negative values. CONCLUSION Acarbose tablet is bioinequivalent to the reference tablet.This might be related to acarbose dose, the 50 mg dose of acarbose tablet is inadequate. Pharmacodynamics parameters which is suitable to demonstrate acarbose bioequivalence might also need to be optimized.
关键词
阿卡波糖 /
生物等效性 /
药效学评价
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Key words
acarbose /
bioequivalence /
pharmacodynamics evaluation
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黄明, 张全英, 徐凤华, 王蒙, 周文佳.
以药效学参数为终点指标评价中国人群阿卡波糖片人体生物等效性[J]. 中国药学杂志, 2019, 54(16): 1323-1327 https://doi.org/10.11669/cpj.2019.16.009
HUANG Ming, ZHANG Quan-ying, XU Feng-hua, WANG Meng, ZHOU Wen-jia.
Bioequivalence Evaluation of Acarbose Tablet in Healthy Chinese Volunteers with Pharmacodynamic Endpoints[J]. Chinese Pharmaceutical Journal, 2019, 54(16): 1323-1327 https://doi.org/10.11669/cpj.2019.16.009
中图分类号：
R969
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参考文献
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脚注
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基金
苏州市药学会-江苏恒瑞临床药学科研基金项目资助(Syhky201807)
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