甲氧苄啶羟丙基-β-环糊精包合物的制备及在家兔体内的药代动力学研究  

Preparation of trimethoprim-hydroxypropyl-β-cyclodextrin inclusion complex and its pharmacokinetics in rabbit

作　　者：邹玉珠[1] 符华林[1] 张伟[1] 唐文[1] 周凤[1] 

机构地区：[1]四川农业大学动物医学院,四川雅安625014

出　　处：《中国兽医科学》2010年第12期1285-1290,共6页Chinese Veterinary Science

基　　金：教育部"长江学者和创新团队发展计划"创新团队项目(IRT0848)

摘　　要：以溶液搅拌法制备甲氧苄啶羟丙基-β-环糊精包合物,分别采用差示扫描量热法、薄层法和相溶解度法对包合物进行鉴定;10只家兔分别单剂量肌肉注射甲氧苄啶和包合物,检测血药浓度;用DAS2.0药代动力学程序计算药代动力学参数。结果成功制得包合物;家兔单剂量注射甲氧苄啶和包合物后,主要的药代动力学参数Cmax分别为10.267 mg/L±0.025 mg/L和14.932 mg/L±0.060 mg/L,tmax分别为1.5 h和1.0h,AUC0→t分别为41.282 mg/L.h±0.170 mg/L.h和62.729 mg/L.h±0.102 mg/L.h。结果显示,包合后达峰时间缩短,峰浓度显著提高,相对生物利用度为153.9%。证实,高效液相色谱法准确、灵敏,适用于甲氧苄啶血浆浓度的测定;制备的甲氧苄啶包合物与甲氧苄啶相比,体内吸收速度与吸收程度显著提高。The aim of this study was to establish HPLC method for determination of plasma trimethoprim concentration,prepare the inclusion complex of trimethoprim-hydroxypropyl-β-cyclodextrin（TMP-HP-β-CD） and evaluate its pharmacokinetic behavior in rabbits.TMP-HP-β-CD inclusion complex was prepared using a solution-stiring method.The identification of the inclusion complex was carried out by the following methods separately：differential scanning calorimeter,thin layer chromatography and phase solubility method.The blood samples from rabbits intramuscularly receiving a single dose of either TMP solution of TMP-HP-β-CD solution were collected to measure plasma TMP concentrations by HPLC.The pharmacokinetics parameters were analyzed with DAS2.0 software.In result,the inclusion complex was successfully prepared.The major pharmacokinetics parameters of TMP and TMP-HP-β-CD were shown as Cmax of 10.267mg/L±0.025mg/L vs.14.932mg/L±0.060mg/L,tmax of 1.5h vs.1.0h,and AUC0→t of 41.282mg/L·h±0.170mg/L·h vs.62.729mg/L·h±0.102mg/L·h,respectively.The relative bioavailability of TMP-HP-β-CD was 153.9%.In conclusion,HPLC was suitable for the determination of trimethoprim plasma concentration in rabbit.The TMP-HP-β-CD inclusion complex can significantly improve the solubility and increase bioavailability of TMP in rabbit.

关 键 词：甲氧苄啶 羟丙基-Β-环糊精 包合物 家兔 药代动力学 高效液相色谱法 

分 类 号：S859.7[农业科学—临床兽医学]