羟喜树碱纳米乳在大鼠体内的药代动力学研究  

Pharmacokinetics of Hydroxycamptothecin Microemulsions in Rats

作　　者：龚明涛[1] 张钧寿[1] 戴晓鸣[2] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]中国药科大学生理学教研室,南京210009

出　　处：《中国药科大学学报》2004年第4期324-327,共4页Journal of China Pharmaceutical University

摘　　要：目的 :研究 10 羟喜树碱水针和纳米乳在大鼠体内的药动学特征。方法 :建立同时测定大鼠血浆中 10 羟喜树碱羧酸盐和内酯两种存在形式的HPLC 荧光检测法 ,大鼠股静脉注射给药后于不同时间点进行眼眶静脉丛取血 ,测定血浆中两种形式的血药浓度 ,并用 3P97药动学程序对血药浓度进行处理。结果 :10 羟喜树碱羧酸盐和内酯形式可与血浆中的其它成分较好地分离 ,在 10～ 10 0 0 0ng/ml的血药浓度范围内呈良好的线性关系。 10 羟喜树碱水针和纳米乳两种制剂大鼠静脉给药后总药物的AUC无显著性差异 ,但前者大部分以羧酸盐形式存在 ,而后者大部分以内酯形式存在。结论 :与水针相比 ,10 羟喜树碱制备成纳米乳制剂后可大大提高大鼠体内其药理活性较高的内酯形式的血药浓度。AIM:To study the pharmacokinetic characteristics of microemulsions containing 10-hydroxycamptothecin(HCPT) in rats. METHOD:A reversed-phase high-performance liquid chromatography with fluorescence detection was developed and validated for simultaneous analysis of HCPT in lactone and carboxylate form in rat plasma. The plasma concentrations of HCPT in both forms were detected at various times following a single iv dose of 5 mg/kg HCPT. The data were processed with the pharmacokinetic software 3P97. RESULT:A good separation of HCPT in lactone and carboxylate forms with other substances in plasma was obtained. The assay was liner over the range of 10～10000 ng/ml. When the concentration of both forms of HCPT was added together,there was no significant difference of AUC between normal injection and microemulsion. However,HCPT mainly remains in the carboxylate form after administration of normal injection while a major part of HCPT was obtained in lactone form after iv. microemulsion. CONCLUSION: Compared with reference injection,the microemulsion can greatly increase the plasma concentration of lactone form,which possesses a much stronger anticancer activity.

关 键 词：羟喜树碱 纳米乳 药动学 血药浓度 

分 类 号：R96[医药卫生—药理学]