硝克柳胺在大鼠体内的药代动力学  

Pharmacokinetics of nicousamide in rats

作　　者：盛莉[1] 牛长群[1] 扈金萍[1] 陈晖[1] 李燕[1] 

机构地区：[1]中国医学科学院中国协和医科大学药物研究所,北京100050

出　　处：《山西医科大学学报》2007年第7期599-603,共5页Journal of Shanxi Medical University

基　　金：国家科技攻关973基金资助项目(2004CBH518905);北京市重大科技项目(H020220060910)

摘　　要：目的研究大鼠口服不同剂量硝克柳胺后的药代动力学和生物利用度,为临床研究和应用提供参考依据。方法本研究建立了HPLC-UV方法测定血浆硝克柳胺浓度。大鼠分别口服硝克柳胺(30,100,300mg/kg)、静脉注射硝克柳胺(10mg/kg)进行药代动力学和绝对生物利用度研究。结果硝克柳胺在20-2000ng/ml呈良好线性关系(R2=0.9999),日内和日间精密度RSD均小于10%,回收率为95%-105%之间。大鼠口服不同剂量硝克柳胺后,AUC和Cmax与剂量之间线性相关。硝克柳胺自雌鼠体内吸收和消除均明显快于雄鼠。雄鼠口服硝克柳胺后生物利用度为1.34%,雌鼠为0.67%。结论HPLC-UV法具有灵敏度高、可靠和专属性强的特点,可用来测定大鼠血浆硝克柳胺的浓度。大鼠口服硝克柳胺(30-300mg/kg)体内代谢为线性动力学过程,且存在明显性别差异,绝对生物利用度较低。Objective To develop a rapid and sensitive HPLC-UV method for determining nicousamide in plasma, and to study the pharmacokinetic properties of nicousamide in rats. Methods Plasma nicousamide was detected by HPLC-UV. Pharmacokinetics was studied in rats at an oral dose of 30, 100, 300 mg/kg of nicousamide or an intravenous dose of 10 mg/kg, respectively. Results Calibration curves were linear over the concentration range of 20 - 2 000 ng/ml of nicousamide with the intra- and inter-day precisions less than 10%. Recovery of nicousamide in plasma was 95% - 105%. Following the oral doses of 30, 100, 300 mg/kg, AUC and Cmax increased proportionally with doses. Nicousamide was absorbed and eliminated more rapidly in female than in male rats. The absolute bioavailability of nicousamide after ig administration was 1.34 % in male rats and 0.67 % in female rats. Conclusion The HPLC-UV method for determining nicousamide in rat plasma is sensitive, stable and rapid. Nicousamide in rats at single oral doses of 30 - 300 mg/kg is a linear pharmacokinetics. The absolute bioavailability of nicousamide is lower.

关 键 词：药代动力学 硝克柳胺 HPLC 生物利用度 

分 类 号：R917[医药卫生—药物分析学]