Study on the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats  

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（英文）

作　　者：Dujuan Zhang Keguang Chen Rui Zhang Guiyan Yuan Benjie Wang Ruichen Guo 张杜娟;陈克广;张蕊;袁桂艳;王本杰;郭瑞臣(济南市妇幼保健院药剂科,山东济南250001;山东大学齐鲁医院临床药理研究所,山东济南250012)

机构地区：[1]Department of pharmacy of Jinan maternity and child care hospital, Jinan 250001, China [2]Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan 250012, China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2018年第1期22-30,共9页中国药学（英文版）

摘　　要：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 AUC0–24 and Cmax 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 Tmax and t1/2.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 AUC0–12 and Cmax of 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.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),Tmax和t1/2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：ROSUVASTATIN REPAGLINIDE PHARMACOKINETICS Drug-drug interaction Liver distribution 

分 类 号：R969.1[医药卫生—药理学]