摘要
目的: 探讨地塞米松 葡聚糖 (平均Mr76 000)前体药在大鼠体内的药代动力学.方法: 地塞米松 (dexamethason,Dex)及其前体药按 5μmol/kg给大鼠ig,采用高效液相色谱法监测前体药在大鼠胃肠道不同部位释放出Dex的动力学过程及血药浓度.结果: Dex前体药ig后,Dex主要分布在盲肠和结肠内容物及黏膜中,在胃及小肠近端的内容物中检测不到药物释放,Dex吸收缓慢,tpeak为 6 2h,血浆药物峰浓度Cmax为 149μg/L,AUC为 1364μg/(h·L).Dexig后,药物主要分布在胃、小肠近端及小肠远端内容物及黏膜中,药物吸收迅速,tpeak为 2 2h,血浆药物峰浓度Cmax为 2120μg/L,AUC为11 875μg/(h·L).结论: Dex 葡聚糖前体药可将Dex转运到盲肠和结肠,显著减少了Dex的吸收,提高了结肠局部药物浓度,是一种具有良好应用前景的治疗炎症性肠病的药物.
AIM: To study the pharmacokinetics of dexamethasone-succinate-dextran (average M r of dextran 76 000) prodrug in rats.METHODS: Dexamethasone (Dex) and the prodrug were orally administered to rats at the dose of 5 μmol/kg ,respectively.The drug in the plasma and in the content of different parts of the rat GI tract was determined by high performance liquid chromatography (HPLC). RESULTS: Dex was mainly released in the contents and mucosa of cecum and colon after oral administration of prodrug and its absorption was reduced significantly.The peak time,peak concentration and AUC were 6.2 h,149 μg/L and 1364 μg/(h·L),respectively.Free Dex was found mainly in the contents and mucosa of the stomach,and proximal and distal small intestine after oral administration.The peak time,peak concentration and AUC were 2.2 h,2120 μg/L and 11 875 μg/(h·L),respectively.CONCLUSION: Dex can be specifically delivered to the cecum and colon by using dexamethasone-succinate-dextran prodrug.The absorption of Dex is reduced significantly and the drug concentration in colon increases.The prodrug holds a potential for the treatment of inflammatory bowel disease.
出处
《第四军医大学学报》
北大核心
2005年第6期488-491,共4页
Journal of the Fourth Military Medical University
基金
国家"863"计划资助项目(2004AA2Z3160)
