硝克柳胺在大鼠体内的药代动力学

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（R^2=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。

Pharmacokinetics of nicousamide in rats

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.