大鼠体内瑞舒伐他汀和瑞格列奈药动学和肝脏分布相互作用研究

doi:10.5246/jcps.2018.01.003

摘要/Abstract

摘要：

本文主要研究大鼠体内瑞舒伐他汀和瑞格列奈在药动学和肝脏分布方面的相互作用。发现健康Wistar大鼠连续7天灌服瑞格列奈(0.5 mg/kg, 1 mg/kg and 2 mg/kg)后给予瑞舒伐他汀(10 mg/kg),与对照组相比, 瑞舒伐他汀AUC_0–24和C_max显著提高(P<0.01), CL/F显著降低(P<0.01), T_max和t_1/2变化不明显,肝脏浓度显著减低(P<0.01)。大鼠连续7天灌服瑞舒伐他汀(20 mg/kg)后给予瑞格列奈(1 mg/kg), 与对照组相比, 瑞格列奈AUC_0–12和C_max显著提高(P<0.05), CL/F显著降低(P<0.01), 肝脏浓度显著降低(P<0.01)。瑞格列奈可影响瑞舒伐他汀药动学和肝脏分布, 瑞舒伐他汀也可影响瑞格列奈的药动学和肝脏分布。

关键词: 瑞舒伐他汀, 瑞格列奈, 药动学, 药物相互作用, 肝脏分布

Abstract:

In the present study,we aimed to investigate the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats.Coadministration of repaglinide (0.5 mg/kg, 1 mg/kg and 2 mg/kg) for 7 d significantly increased the AUC_0–24 and C_max of rosuvastatin (P<0.01), but dramatically decreased the CL/F of rosuvastatin (P<0.01) after a single dose of rosuvastatin (10 mg/kg). There were no obviously changes in the parameters of T_maxand t_1/2. Coadministration of repaglinide also decreased the liver distribution of rosuvastatin (P<0.01). Coadministration of rosuvastatin (20 mg/kg) for 7 days significantly increased the AUC_0–12 and C_maxof repaglinide (P<0.05), and decreased the CL/F of repaglinide (P<0.01) after a single dose of repaglinide (1 mg/kg). The liver distribution of repaglinide was also decreased (P<0.01). Our animal study indicated that repaglinide could significantly affect the pharmacokinetics and liver distribution of rosuvastatin in rats and vice versa.

Key words: Rosuvastatin, Repaglinide, Pharmacokinetics, Drug-drug interaction, Liver distribution

中图分类号:

R969.1

Supporting:

张杜娟, 陈克广, 张蕊, 袁桂艳, 王本杰, 郭瑞臣. 大鼠体内瑞舒伐他汀和瑞格列奈药动学和肝脏分布相互作用研究[J]. 中国药学(英文版), 2018, 27(1): 22-30.

Dujuan Zhang, Keguang Chen, Rui Zhang, Guiyan Yuan, Benjie Wang, Ruichen Guo. Study on the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(1): 22-30.

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