川芎嗪自乳化缓释固体分散体在兔体内的药动学研究

Pharmacokinetics Study of Tetramethylpyrazine Self -emulsifying Sustained -release Solid Dispersion in Rabbits

目的研究川芎嗪自乳化缓释固体分散体(TMP-SESD)及普通缓释固体分散体(TMP-SD)在兔体内的药动学特征。方法 6只新西兰兔随机分为2组,采用自身交叉对照实验,单剂量口服TMP-SESD和TMP-SD后,采用高效液相色谱法测定血浆中TMP的浓度,DAS2.1数据处理软件计算药动学参数。结果 TMP-SESD和TMP-SD给药后,药动学参数如下:tmax分别为4 h和6 h;Cmax分别为(3.217±0.4581)mg.L-1和(6.105±0.298)mg.L-1;AUC0-∞分别为(63.877±3.786)mg.L-1.h和(39.067±2.971)mg.L-1.h;与TMP-SD比较,TMP-SESD的相对生物利用度为(163.5±9.58)%。结论家兔体内川芎嗪的药动学规律均符合一级吸收二室模型,与普通缓释固体分散体相比,自乳化缓释固体分散体Cmax和AUC0-∞均较高,说明自乳化缓释固体分散体能显著提高药物的生物利用度。

Objective To compare pharmacokinetics and relative bioavailability of Tetramethylpyrazine self-emulsify-ing sustained-release solid dispersion （TMP-SESD） and Tetramethylpyrazine sustai^ed-release solid dispersion （TMP-SD） in rabbits. Methods Single dose of TMP-SESD or TMP-SD was orally given to 6 rabbits in a randomized crossover control study. The TMP concentration in plasma was determined by high performance liquid chromatography, and pharmacokinetic parameters and relative bioavailability were calculated by DAS 2.1 software. Results The main pharmacokinetic parameters for TMP-SESD and TMP-SD were as follows： tmax was 4 h and 6 h, Cmax was 3.217 ：t： 0.4581 mg·L^-1 and 6.105 ± 0.298 mg·L^-1; AUC0-∞ was 63.877 ± 3.786 mg·L^-1·h and 39.067 ± 2.971 mg·L^-1·h, re spectively. The relative bioavailability of TMP-SESD was （163.5 ± 9.58） % as compared with TMP-SD. Conclusion The pharmacokinetic parameters of TMP in rabbits accord with the two-compartment model, and Cmax and AUC0-∞ of TMP-SESD are all higher than those of TMP-SD, and TMP-SESD has a higher bioavailability during the first absorp-tion after TMP-SESD or TMP-SD administration.