雷替曲塞联合促吸收剂的体外评价及其结肠靶向片在胃肠道的吸收与分布  

In vitro pharmacodynamics of raltitrexed combined with absorption enhancers and in vivo gastrointestinal absorption and distribution of its colon-targeted tablet

作　　者：那馨竹[1] 于永[1] 黄园[1] 尹宗宁[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《中国医院药学杂志》2015年第22期2027-2030,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:考察加入卡波姆934P和丙磺舒后雷替曲塞对人结肠癌细胞株HT-29的抑制增强作用,以及雷替曲塞结肠靶向片的胃肠道分布靶向性和促吸收特性。方法:采用MTT法考察雷替曲塞及其联合卡波姆934P与丙磺舒对HT-29细胞的体外抑制效果;并对比考察雷替曲塞的4种口服制剂即溶液、普通片、普通包衣片与结肠靶向片经口服给药后,药物在大鼠胃肠道内的吸收分布情况。结果:体外细胞毒性实验显示,雷替曲塞及其与卡波姆934P和丙磺舒联合使用均能抑制HT-29细胞的生长,而后者对HT-29细胞的抑制效果更加显著;大鼠体内胃肠道吸收与分布实验结果显示,供试的结肠靶向片能在大肠部位有效的释放药物并显著地促进药物的吸收摄取,与溶液剂、普通片和普通包衣片相比,药物在大肠内的累计分布量(AUC0-15 h)分别提高了6.54倍、7.30倍和5.49倍(P<0.05),雷替曲塞的血药浓度-时间曲线下面积(AUC0-24 h)也有相应的增加。结论:卡波姆934P和丙磺舒的加入能增加雷替曲塞对HT-29细胞的抑制作用,且制备的雷替曲塞结肠靶向片靶向性强,药物在结肠处的吸收与摄取量大。OBJECtIVE To investigate enhanced depression efficiency of raltitrexed added with carbomer 934P and probene- cid on human colorectal cancer cell line HT-29 in vitro and target efficiency and enhanced absorption of raltitrexed colon-targe- ted tablets in gastrointestinal tract. METHODS MTr assays were used to evaluate depression efficiencies of raltitrexed, raltit- rexed-earbomer 934P, raltitrexed.probenecid and raltitrexed-carbomer 934P probenecid on human colorectal cancer cell line HT- 29 in vitro, while drug absorption and distribution of solution, common tablets （uncoated）, coated common tablets and colon- targeted tablets in gastrointestinal tract were examined in Wistar rats. R^ULTS Inhibition rate of raltitrexed-carbomer 934P- probenecid, as proved in vitro, was higher than that of raltitrexed. Moreover, compared with solution, common tablets （un- coated）, coated common tablets, area under concentration-time curve （AUC0 15h） of drug in large intestine tissues was in- creased with ratios of 6. 54, 7. 30 and 5.49（P〈0. 05） and area under concentration-time curve （AUCo 24h） of the drug in blood was increased. CONCLUSION When combining with carbomer 934P and probeneeid, depression efficiency of ra[tirexed is higher on human colorectal cancer cell line HT-29 in vitro and the raltitrexed colon-targeted tablets show as high target efficien- cy and absorption in gastrointestinal tract.

关 键 词：雷替曲塞 卡波姆934P 丙磺舒 结肠靶向片 

分 类 号：R961[医药卫生—药理学]