| 健康志愿者二甲双胍缓释片群体药动学模型的初步研究 |
| 投稿时间：2012-12-17 修订日期：2013-04-08 点此下载全文 |
| 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].药学实践杂志,2013,31(5):338~343,346 |
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| 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). |
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| 中文摘要: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。 |
| 中文关键词:二甲双胍 群体药动学 液相色谱质谱联用 |
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| Preliminary study on population pharmacokinetic model of metformin sustained-release tablets in healthy subjects |
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| 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. |
| keywords:metformin population pharmacokinetics (PPK) LC-MS/MS |
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