吲哚美辛及其共聚维酮固体分散体在大鼠体内药动学比较研究  

Pharmacokinetics of indomethacin and its solid dispersion with Co-PVP as carrier in rats

作　　者：王转[1,2] 张妙恽[2] 尹东东[2] 魏广力[2] 王杏林[2] 

机构地区：[1]天津中医药大学,天津300193 [2]天津药物研究院有限公司释药技术与药代动力学国家重点实验室,天津300193

出　　处：《中南药学》2015年第12期1259-1262,共4页Central South Pharmacy

基　　金：国家重大新药创新项目(编号:2014ZX09507005-002)

摘　　要：目的以吲哚美辛为对照,研究吲哚美辛共聚维酮固体分散体在SD大鼠体内药动学过程。方法将12只SD大鼠随机分成3组,每组4只,雌雄各半。3组分别灌胃给予吲哚美辛、吲哚美辛共聚维酮物理混合物、吲哚美辛共聚维酮固体分散体(以吲哚美辛计1.78 mg·kg^(-1))。LC-MS/MS法测定吲哚美辛在大鼠体内血药浓度变化。采用Win Nonlin 6.3选取非房室模型法进行药物代谢动力学参数计算。结果健康SD大鼠经灌胃给予吲哚美辛及其固体分散体制剂后,其AUC0~t分别为(141±22.5)和(135±33.7)μg·h·m L^(-1);Cmax分别为(8.88±2.23)和(15.0±1.77)μg·m L^(-1);tmax分别为(2.83±1.66)和(0.208±0.125)h。结论以共聚维酮为载体制备的吲哚美辛固体分散体在大鼠体内能显著缩短达峰时间,增加血浆峰浓度。Objective To study the pharmacokinetics of indomethacin solid dispersion with Co-PVP as carrier in SD rats and compare with indomethacin. Methods Twelev SD rats（n = 12） were randomly divided into 3 groups（n =4） with half male and half female. The SD rats were intragastrically administrated indomethacin, indomethacin-CoPVP physical mixture and indomethacin-Co-PVP solid dispersion respectively（in the indomethacin dosage of 1.78 mg·kg-（-1））. The plasma concentration of indomethacin was determined by LC-MS/MS. All pharmacokinetic parameters were processed by non-compartmental analysis with Win Nonlin 6.3 software. Results After intragastrically administration, the main pharmacokinetic parameters of indomethacin and its solid dispersion in healthy SD rats were as follows： AUC0 - t（141±22.5） and（135±33.7） μg·h·m L-（-1）, Cmax（8.88±2.23） and（15.0±1.77） μg·m L-（-1）, tmax（2.83±1.66） and（0.208±0.125） h. Conclusion The solid dispersion with Co-PVP as carrier significantly shortens the tmax and increases the Cmax.

关 键 词：吲哚美辛 固体分散体 共聚维酮 药动学 LC-MS/MS 

分 类 号：R96[医药卫生—药理学]