【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。更多还原

【Abstract】 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.更多还原