泼尼松龙葡聚糖(2万)前体药物的大鼠结肠定位转释作用  

Colon-Specific Delivery Release of PL-Dextran(20 000) Prodrug in the Rat GI Tract

作　　者：周瑾[1] 梅其炳[2] 周四元[2] 李平[1] 贺建荣[1] 

机构地区：[1]唐都医院药剂科,西安710038 [2]药理学教研室,西安710032

出　　处：《医药导报》2003年第5期297-299,共3页Herald of Medicine

摘　　要：目的 :探讨泼尼松龙葡聚糖 ( 2万 )前体药物在大鼠胃肠道的结肠定位释放作用 ,为寻找理想的炎症性肠病治疗药物奠定基础。方法 :将泼尼松龙葡聚糖 ( 2万 )前体药物按 3 0 μmol·kg 1 的泼尼松龙剂量给大鼠灌胃 ,采用高效液相色谱法 (HPLC)检测大鼠胃肠道不同部位内容物、黏膜中泼尼松龙的动态分布以及血药浓度的变化 ,同时与同等剂量的游离泼尼松龙比较 ,并根据所测结果计算药物转运指数 (DDI)。结果 :前体药物主要是在盲肠和结肠释放出活性药物 ,而游离泼尼松龙主要是在上消化道释放药物 ,前体药物的血药浓度比游离泼尼松龙低 ,且达峰时间长。前体药物在大鼠盲肠黏膜中的药物DDI为 6.464。结论 :泼尼松龙葡聚糖 ( 2万 )前体药物的DDI较高 ,具有较好的结肠定位转释特异性 ,有可能成为一种有应用前景的结肠炎治疗药物。Objective:To observe colon specific delivery release of PL dextran(20 000) prodrug in the rat GI tract for seeking new drug to treat inflammatory bowel diseases. Method:PL prodrug and PL were administrated respectively to rats by oral gavage at the dose of 30 μmol·kg 1 . The distribution of PL in the contents and mucosa of different parts of the rat GI tract between different interval and the fluctuation of PL concentration in plasma were determimed by HPLC. Drug delivery index (DDI) was calculated. Results:PL was mainly released in cecum and colon contents or mucosa after gastric administration of PL prodrug, while PL was mainly distributed in stomach, PSI and DSI contents or mucosa after administration of free PL at the same dosage. The DDI of prodrug was 6.464 in the cecal mucos of the rat. Conclusion:It seems that the PL dextran(20 000) prodrug has a potential for the treatment of colitis.

关 键 词：泼尼松龙葡聚糖(2万) 泼尼松龙 前体药物 结肠定位转释作用 

分 类 号：R969.1[医药卫生—药理学]