雾化吸入羟基喜树碱在肺癌小鼠体内药动学和组织分布  

Study on the pharmacokinetics and tissues distribution of aerosol delivery of hydroxycamptothecin in mice with lung cancer

作　　者：胡文晋[1] 胡巍[2] 张超[3] 方芸[2] 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院,江苏南京210029 [2]南京大学医学院附属鼓楼医院,江苏南京210008 [3]苏州市药品检验所,江苏苏州215000

出　　处：《中国医院药学杂志》2013年第2期103-107,共5页Chinese Journal of Hospital Pharmacy

基　　金：南京市医学科技发展课题(编号:YKK08052)

摘　　要：目的:研究雾化吸入羟基喜树碱(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种不同结构在肺癌小鼠体内的药动学与组织发布。方法:建立HPLC-FLD法测定小鼠血浆及组织中L型及C型HCPT的药物浓度。分析雾化吸入给药后血浆与肺脏、心脏、肝脏、肾脏中药动学参数,并对雾化吸入给药后血浆与组织中的L/C平衡参数进行比较。结果:HCPT的线性关系良好,日内和日间精密度、回收率均符合生物样品的分析要求。雾化吸入HCPT,血浆和各个脏器中均有C-HCPT转换为L-HCPT,肺组织中HCPT显著大于血浆和其他组织。结论:雾化吸入给药具有一定的靶向性,可提高肺组织中L型药物浓度,更有利于肺癌的治疗。OKIECTIVE To study the pharmacokinetic and tissue distribution of L-HCPT and C-HCPT in mice with lung cancer after aerosol inhalation of HCPT. METHODS HPLC-FLD was used to determine the L HCPT and C-HCPT in plasma and tissues of mice. The regulation on lactone/carboxylate equilibrium of hydroxycamptothecin was compared, analyzed and es timated for pharmacokinetic parameters in plasma and tissues of mice after aerosol inhalation. RESULTS The recovery,the in tra-day RSD and the inter-day RSD of L-HCPT met the requirement of detection. The concentrations of L-HCPT were im proved after aerosol administration, especially in lung, which was the highest among that in plasma and tissues. CONCLU- SION Aerosol inhalation possessed a certain degree of lung targeting, it could rise the concentration of LHCPT in lung, which was good for the therapy of lung cancer.

关 键 词：肺癌 羟基喜树碱 雾化吸入 药动学 组织分布 

分 类 号：R979.1[医药卫生—药品]