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[霉酚酸肠肝循环的药代动力学模型]

[Pharmacokinetic model for the enterohepatic circulation of mycophenolic acid].

作者信息

Jiao Zheng, Shen Jie, Zhong Long-jin, Yu Yun-qiu, Zhong Ming-kang

机构信息

Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Yao Xue Xue Bao. 2006 Mar;41(3):272-6.

Abstract

AIM

To develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA).

METHODS

Twenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model.

RESULTS

The proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations.

CONCLUSION

The established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

摘要

目的

建立霉酚酸(MPA)肝肠循环的药代动力学模型。

方法

20名健康志愿者口服单剂量500mg吗替麦考酚酯。在48小时内采集血浆样本,采用高效液相色谱法测定MPA浓度。基于生理学和生物药剂学考虑建立药代动力学(PK)模型,并使用非线性混合效应模型获得PK参数。

结果

所提出的模型除中央室之外还包括肠室和胆囊室。所建立模型预测的时间-浓度曲线以及AUC0-t、Cmax、Tmax与观测值一致。

结论

所建立的模型很好地定义了MPA的处置情况,可为进一步的临床研究提供有用的方法。

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