普伐他汀在健康受试者中的生理药动学研究

发布时间：2018-03-16 00:30

本文选题：普伐他汀　切入点：健康受试者　出处：《中国新药杂志》2015年13期 　论文类型：期刊论文

【摘要】：目的:考察口服普伐他汀在健康受试者体内的生理药动学(PBPK)模型。方法:收集文献报道的理化性质和体外酶促动力学数据,结合人口统计学资料,建立普伐他汀在人体的生理药动学模型。预测单剂量口服10,20,40 mg普伐他汀的血药浓度-时间曲线,并用文献药时曲线和药动学参数实测值验证已建立的模型,预测各剂量在不同组织内的分布情况。结果:本文建立的生理药动学模型中,药时曲线预测值与实测值相符合,预测的不同剂量药动学参数(AUC,Cmax,Tmax)与实测值基本一致(倍数误差1.5),模型准确可靠。模型预测结果显示,普伐他汀分布在各组织中,其中肺和心脏分布较多,Cmax分别为(8.14,33.23,71.64ng·m L-1),(7.47,29.91,64.93 ng·m L-1);脑和肌肉分布较少,Cmax分别为(5.60,21.39,46.99 ng·m L-1),(5.03,18.93,43.46 ng·m L-1)。结论:普伐他汀主要分布在肺和心脏,脑和肌肉分布较少,3个剂量组的组织分布趋势相同,含量呈剂量依赖性上升。
[Abstract]:Objective: to investigate the physiological pharmacokinetics of pravastatin in healthy volunteers. Methods: the physical and chemical properties and in vitro enzymatic kinetic data of pravastatin were collected and combined with demographic data. To establish a physiological pharmacokinetic model of pravastatin in human body, to predict the plasma concentration-time curve of pravastatin at a single dose of 10 ~ 20mg pravastatin, and to verify the established model with the drug time curve in literature and the pharmacokinetic parameters. Results: in the physiological pharmacokinetic model established in this paper, the predicted value of drug time curve coincided with the measured value. The predicted pharmacokinetic parameters were basically consistent with the measured values (multiple error was 1.5%, the model was accurate and reliable. The predicted results showed that pravastatin was distributed in all tissues. Cmax of lung and heart were 8.14 ~ 33.2371.64 ng 路ml ~ (-1), 64.93 ng 路m ~ (-1) ng 路m ~ (-1) and 5.60 ~ 21.39 ~ 46.99 ng 路m ~ (-1) ng 路m ~ (-1), respectively. Conclusion: pravastatin is mainly distributed in lung and heart, brain and muscle are less, and tissue distribution trend is the same in three dose groups. The content increased in a dose-dependent manner.
【作者单位】：天津市第四医院;天津市第一中心医院;天津医科大学;
【分类号】：R969.1

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