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LC-MS法研究科罗索酸在正常及糖尿病模型大鼠血浆中的药代动力学

Pharmacokinetic study of corosolic acid in normal rats and diabetic rats by LC-MS

  • 摘要: 建立科罗索酸在正常及糖尿病大鼠血浆中LC-MS检测方法,同时比较其药代动力学差异。采用高脂饮食结合低剂量链脲佐菌素诱发大鼠糖尿病模型,灌胃给予两组大鼠科罗索酸(170 mg/kg),于给药前后不同时间点从眼底静脉丛取血,测定血药浓度计算药代动力学参数。科罗索酸在正常及糖尿病大鼠体内的吸收均呈现双峰形式,大鼠在糖尿病病理状态下科罗索酸的cmax、AUC0-24 h明显增加,t1/2显著延长,CL/F显著减小,提示糖尿病会明显改变科罗索酸在大鼠体内的药代动力学行为,可为科罗索酸的临床应用提供参考。

     

    Abstract: An LC-MS method for quantification of corosolic acid in the plasma of rats was developed to investigated the pharmacokinetics of corosolic acid in normal and diabetic rats. Corosolic acid(170 mg/kg)was orally administered to normal rats and the diabetic rats induced by streptozotocin respectively. Blood samples were obtained from the oculic horioideae vein before and after dosing at selected intervals. The concentrations of corosolic acid were determined by LC-MS and the concentration-time data were analyzed by non-compartmental method using DAS 2. 0 software. Doublet peaks were shown in both normal and diabetic rats. The cmax and AUC0-24 h were significantly increased, t1/2 was remarkably prolonged and CL/F was observably decreased compared with those in the normal rats. The status of diabetes mellitus could alter the pharmacokinetics of corosolic acid in rats. The result obtained from the present study could provide reference for the evaluation of its relevant clinical efficacy.

     

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