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.
出处
《中南药学》
CAS
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)
