甲基斑蝥胺灌胃和静脉注射给药的药代动力学研究

Pharmacokinetics of N-methylcantharidimide after intragastral and intravenous administration

目的：研究甲基斑蝥胺（-Nmethylcantharidimide,NMC）灌胃和静脉注射给药后在大鼠体内的药代动力学以及在小鼠肝肾组织的分布。方法：大鼠灌胃和静脉注射NMC后,用RP-HPLC法测定不同时间血浆中的药物浓度,并采用3P97计算药代动力学参数。小鼠灌胃和静脉注射NMC后,同法测定不同时间肝、肾组织中的药物浓度。结果：灌胃和静脉注射后,以梯形法计算AUC0-∞分别为（81±10）μg.h/mL和（143±19）μg.h/mL,拟合血药浓度数据为单室模型。各时间点NMC在肝脏中的浓度灌胃给药均大于静脉注射,而肾脏中的浓度除最后一个时间点（3 h）外,灌胃给药均低于静脉注射给药。结论：NMC的血浓数据拟合为单室模型,灌胃给药的绝对生物利用度为57%,但在增加肝癌疗效和降低肾毒性方面可能优于静脉注射给药。

Aim：To study the pharmacokinetics and tissue distribution of N-methylcantharidimide （NMC） respectively in rats and in mice after intragastral and intravenous administration. Methods： Plasma concentrations of NMC in rats after ig and iv administration were determined by RP-HPLC. The phannacokinetic parameters were calculated by 3P97 program. NMC concentrations in liver and kidney tissues of mice were determined in the same way. Results： After ig and iv administration, AUC0-∞ were （81 ± 10） and （143± 19） μg·h/mL respectively, calculated by trapezoidal rule, and plasma concentration-time curves of NMC were both fitted to single-compartment model. The concentrations of NMC in fiver after ig dosing were more than those after iv at all time points. However, the concentrations in kidney after ig dosing were lower than those affer iv dosing except the last time point （3 h ）. Conclusion： Plasma concentration-time curves of NMC after ig and iv administration were both fitted to single-compartment model. After ig administration,the absolute bioavailabifity was 57%, while the better therapeutic effect on liver cancer and the less renal toxicity than after iv dosing.