氟伐他汀钠缓释片的制备及其Beagle犬体内药动学研究

Study on Preparation of Fluvastatin Sodium Extended-release Tablet and Its Pharmacokinetics in Beagle Dogs

目的制备氟伐他汀钠缓释片,进行体外释放特性以及Beagle犬体内药动学研究。方法以羟丙甲纤维素为缓释材料制备氟伐他汀钠缓释片,测定其体外释放度和Beagle犬口服单剂量及多剂量后的血药浓度,推算药动学参数。结果制备的氟伐他汀钠缓释片体外释放行为相似,口服单剂量和多剂量药动学参数C_(max)分别为(3304.23±1043.30)μg·L^(-1)和(3 760.86±754.77)μg·L^(-1),T_(1/2)分别为(7.37±4.09)h和(6.04±2.63)h,AUC_((0-t))分别为(15 052.91±3 878.01)μg·L^(-1)和(15 374.91±2 712.20)μg·h·L^(-1)。结论制备的氟伐他汀钠缓释片具有较明显的缓释效果,多次给药未出现明显的蓄积现象,表现出良好的安全性。

OBJECTIVE To prepare the fluvastatin extended-release tablet and investigate its pharmacokinetics in Beagle dogs and in vitro release. METHODS Hydroxypropyl methyl cellulose was used as a sustained release material to prepare fluvastatin sodium extended release tablet. The release degree in vitro and the concentration of blood drug after single and multi dose oral administration of Beagle dogs were measured. The pharmacokinetic parameters were calculated. RESULTS The release behavior of fluvastatin extended-release tablets were similar in vitro, Cmax in Beagle dogs after single dose and multi dose oral administration were(3 304.23±1 043.30)μg·L-1 and(3 760.86±754.77)μg·L-1, T1/2 were(7.37±4.09)h and(6.04±2.63)h, AUC(0-t) were(15 052.91±3 878.01)μg·L-1 and(15 374.91±2 712.20)μg·h·L-1. CONCLUSION The fluvastatin extendedrelease tablet shows a significant sustained release effect, and good security but not obvious accumulation phenomenon during repeated administration.