Pharmacokinetic study of dexamethasoneª²succinateª²dextran prodrug in rats

    LIU Xinª²You,ZHOU Siª²Yuan,RAN Yuª²Hua,MEI Qiª²Bing

    Department of Pharmacology,School of Pharmacy,Fourth Military Medical University,Xi¬ðan 710033,China

    ¡¾Abstract¡¿ AIM: To study the pharmacokinetics of dexamethasoneª²succinateª²dextran (average Mr of dextran 76 000) prodrug in rats.METHODS: Dexamethasone (Dex) and the prodrug were orally administered to rats at the dose of 5 ¦Ìmol/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 6ª±2 h,149 ¦Ìg/L and 1364 ¦Ìg/(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 2ª±2 h,2120 ¦Ìg/L and 11 875 ¦Ìg/(h¡¤L),respectively.CONCLUSION: Dex can be specifically delivered to the cecum and colon by using dexamethasoneª²succinateª²dextran 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. ......