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

doi:10.3969/j.issn.1006-0111.2013.05.005

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K_a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。
- 二甲双胍 /
- 群体药动学 /
- 液相色谱质谱联用
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.
- metformin /
- population pharmacokinetics (PPK) /
- LC-MS/MS

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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

doi: 10.3969/j.issn.1006-0111.2013.05.005

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

计量

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

English Abstract

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

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留言板

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

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

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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

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

English Abstract

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

全文HTML

目录

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

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