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健康志愿者二甲双胍缓释片群体药动学模型的初步研究

徐懿萍,  陈冰,  荣征星,  陈红专,  张军东

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文章导航 > 药学实践与服务  > 2013 >  31(5): 338-343,346
徐懿萍, 陈冰, 荣征星, 陈红专, 张军东. 健康志愿者二甲双胍缓释片群体药动学模型的初步研究[J]. 药学实践与服务, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
引用本文: 徐懿萍, 陈冰, 荣征星, 陈红专, 张军东. 健康志愿者二甲双胍缓释片群体药动学模型的初步研究[J]. 药学实践与服务, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
shu
XU Yi-ping, CHEN Bing, RONG Zheng-xing, CHEN Hong-zhuan, ZHANG Jun-dong. Preliminary study on population pharmacokinetic model of metformin sustained-release tablets in healthy subjects[J]. Journal of Pharmaceutical Practice and Service, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
Citation: XU Yi-ping, CHEN Bing, RONG Zheng-xing, CHEN Hong-zhuan, ZHANG Jun-dong. Preliminary study on population pharmacokinetic model of metformin sustained-release tablets in healthy subjects[J]. Journal of Pharmaceutical Practice and Service, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
shu

健康志愿者二甲双胍缓释片群体药动学模型的初步研究

doi: 10.3969/j.issn.1006-0111.2013.05.005
  • 1.

    上海交通大学医学院附属瑞金医院, 上海 200025

  • 2.

    上海交通大学基础医学院药理学教研室, 上海 200025

  • 3.

    上海信谊药厂有限公司药物研究所, 上海 201206

基金项目: 上海市科学技术委员会(10DZ1920803)、科技部重大新药创制专项(2012ZX09303006).

Preliminary study on population pharmacokinetic model of metformin sustained-release tablets in healthy subjects

  • 1.

    School of Medicine, Ruijin Hospital affiliated to Shanghai Jiaotong University, Shanghai 200025, China

  • 2.

    School of Medicine, Shanghai Jiaotong University, Shanghai 200025 China

  • 3.

    Shanghai sine pharmaceutical R&D center, Shanghai 201206 China

  • 摘要: 目的 建立中国健康志愿者服用二甲双胍缓释片的群体药动学(PPK)模型,并研究不同生理因素对二甲双胍药动学参数的影响。 方法 20名中国健康受试者(男性11名、女性9名),单剂量给予二甲双胍缓释片 1 000 mg,收集受试者服药后0~24 h血样标本,建立液相色谱-质谱/质谱(LC-MS/MS)方法测定人血浆二甲双胍浓度,采用非线性混合效应模型(NONMEM)建立二甲双胍的群体药动学(PPK)模型,并探讨生理因素对二甲双胍药动学的影响。 结果 二甲双胍药动学符合一房室模型,清除率(CL/F)、分布容积(Vd/F)和吸收速率常数Ka分别为(95.8±7.46) L/h、(553±45.9) L及(0.596±0.070)/h。引入体重作为CL/F及Vd/F的协变量,使模型显著改善(P<0.05)。 结论 NONMEM法可以用于二甲双胍药动学研究,且体重对二甲双胍清除率存在显著影响。
    Abstract: Objective To establish a population pharmacokinetic (PPK) model of metformin in healthy Chinese subjects, and evaluate the effect of different physiological factors on pharmacokinetic parameters of metformin. Methods A single dose, open label PK study was designed to assess the pharmacokinetics of metformin in healthy Chinese subjects (11 male and 9 female subjects). After 1 000 mg single dose of metformin sustained release tablets being taken, 0~24 h blood samples of each subject were collected. Concentration of plasma metformin was measured by the LC-MS/MS method. Non-compartment analysis was carried out through Winonlin 5.01 software. A PPK model in healthy Chinese subjects was established by using NONMEM. The effects of body weight and other physiological factors on metformin pharmacokinetics were assessed. Results One-compartment model with first-order absorption was the best for the PPK of metformin and the CL/F, Vd/F and Ka were (95.8±7.46) L/h, (553±45.9) L, and (0.596±0.070)/h, respectively. It was proved that, the simulation of model improved significantly (P<0.05) when body weight was used as the covariate of CL/F and Vd/F. Conclusion The PPK method could be used in the metformin pharmacokinetic study and body weight had statistically significant effect on the clearance of metformin.
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  • 收稿日期:  2012-12-17
  • 修回日期:  2013-04-08

健康志愿者二甲双胍缓释片群体药动学模型的初步研究

doi: 10.3969/j.issn.1006-0111.2013.05.005
  • 1. 上海交通大学医学院附属瑞金医院, 上海 200025
  • 2. 上海交通大学基础医学院药理学教研室, 上海 200025
  • 3. 上海信谊药厂有限公司药物研究所, 上海 201206
    • 基金项目:  上海市科学技术委员会(10DZ1920803)、科技部重大新药创制专项(2012ZX09303006).
  • 收稿日期: 2012-12-17
  • 修回日期: 2013-04-08

摘要: 目的 建立中国健康志愿者服用二甲双胍缓释片的群体药动学(PPK)模型,并研究不同生理因素对二甲双胍药动学参数的影响。 方法 20名中国健康受试者(男性11名、女性9名),单剂量给予二甲双胍缓释片 1 000 mg,收集受试者服药后0~24 h血样标本,建立液相色谱-质谱/质谱(LC-MS/MS)方法测定人血浆二甲双胍浓度,采用非线性混合效应模型(NONMEM)建立二甲双胍的群体药动学(PPK)模型,并探讨生理因素对二甲双胍药动学的影响。 结果 二甲双胍药动学符合一房室模型,清除率(CL/F)、分布容积(Vd/F)和吸收速率常数Ka分别为(95.8±7.46) L/h、(553±45.9) L及(0.596±0.070)/h。引入体重作为CL/F及Vd/F的协变量,使模型显著改善(P<0.05)。 结论 NONMEM法可以用于二甲双胍药动学研究,且体重对二甲双胍清除率存在显著影响。

English Abstract

徐懿萍, 陈冰, 荣征星, 陈红专, 张军东. 健康志愿者二甲双胍缓释片群体药动学模型的初步研究[J]. 药学实践与服务, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
引用本文: 徐懿萍, 陈冰, 荣征星, 陈红专, 张军东. 健康志愿者二甲双胍缓释片群体药动学模型的初步研究[J]. 药学实践与服务, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
shu
XU Yi-ping, CHEN Bing, RONG Zheng-xing, CHEN Hong-zhuan, ZHANG Jun-dong. Preliminary study on population pharmacokinetic model of metformin sustained-release tablets in healthy subjects[J]. Journal of Pharmaceutical Practice and Service, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
Citation: XU Yi-ping, CHEN Bing, RONG Zheng-xing, CHEN Hong-zhuan, ZHANG Jun-dong. Preliminary study on population pharmacokinetic model of metformin sustained-release tablets in healthy subjects[J]. Journal of Pharmaceutical Practice and Service, 2013, 31(5): 338-343,346. doi: 10.3969/j.issn.1006-0111.2013.05.005
shu

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