雾化吸入羟基喜树碱内酯/羧酸盐在豚鼠体内的分布  

Investigation of distribution on lactone/carboxylate of hydroxycamptothecin after aerosol inhalation in cavia cobaya

作　　者：胡巍[1] 方芸[1] 张尚锁[2] 

机构地区：[1]南京大学医学院附属鼓楼医院,江苏南京210008 [2]南京中医药大学,江苏南京210029

出　　处：《中国医院药学杂志》2009年第21期1820-1823,共4页Chinese Journal of Hospital Pharmacy

基　　金：江苏省卫生厅奥赛康项目(编号:P200403)

摘　　要：目的:研究比较雾化吸入与静脉注射羟基喜树碱(HCPT)后,主要活性形式内酯型(L-HCPT)和弱活性形式羧酸盐型(C-HCPT)2种不同结构在豚鼠组织及血浆中的分布情况以及两者比值随时间变化的规律。方法:建立HPLC-FLD法测定豚鼠血浆及各组织中内酯型及羧酸盐型羟基喜树碱的药物浓度。比较静脉注射和雾化吸入后豚鼠各组织中内酯/羧酸盐比例随时间的变化。结果:相对于静脉注射途径,采用雾化吸入后,各组织中内酯/羧酸盐的比例均有所提高,尤以肺组织最为明显,肺组织中L-HCPT的AUC占各组织中总的AUC的比值为静脉注射的6.96倍,而肝、肾组织中L-HCPT的AUC占各组织中总的AUC的比值分别下降为静脉注射的33.5%和55%。结论:雾化吸入给药后,在提高肺组织中内酯型药物浓度的同时还能显著降低药物在其他组织的浓度,从而降低了对其他组织的毒性,更有利于肺癌的治疗。OBJECTIVE To study the distribution of LHCPT and C-HCPT in plasma and tissue of cavia cobaya after aero sol inhalation and iv administration of HCPT, and study the regularity on lactone/carboxylate rate with time. METHODS HPLC-FLD was used to determine the concentration of L-HCPT and C-HCPT in plasma and different tissues of cavia cobaya. The regulation on lactone/carboxylate rate of hydroxycamptothecin was compared after aerosol inhalation or iv administration. RESULTS The lactone/carboxylate rate in tissues after aerosol inhalation was higher than that of iv administration,especially in lung; the ratio that AUC of L-HCPT in lung accounted for AUC of overall tissues after aerosol inhalation was 6. 96 times compared to iv administration, but it has descended to 33.5% and 55 % compared to iv administration in liver and kidney. CONCLUSION Aerosol inhalation possessed a certain degree of lung targeting,it could raise the concentration of L-HCPT in lung, at the same time decrease the concentration in any other tissues, accordingly decrease the tissue toxicity, which is good for the curing of lung cancer.

关 键 词：羟基喜树碱 雾化吸入 组织分布 内酯/羧酸盐 

分 类 号：R979.1[医药卫生—药品]