长春胺缓释微丸在Beagle犬体内的药动学特征  

Pharmacokinetics of Vincamine Sustained-release Pellets in Beagle Dogs

作　　者：相琳[1] 曾佳[2] 周游[1] 黄婷[2] 魏莉[3] 

机构地区：[1]大连大学,辽宁大连116622 [2]上海市计划生育科学研究所,国家人口和计划生育委员会计划生育药具重点实验室,上海生殖健康药具工程技术研究中心,上海200032 [3]上海中医药大学,上海201203

出　　处：《中国实验方剂学杂志》2015年第3期85-88,共4页Chinese Journal of Experimental Traditional Medical Formulae

摘　　要：目的:制备长春胺缓释微丸并考察其在Beagle犬体内的药动学特征,为非p H依赖性释放的长春胺缓释制剂研发提供参考。方法:制备酒石酸丸芯,采用流化床混悬液上药法制备长春胺缓释微丸。Beagle犬随机分成2组,单剂量双周期交叉口服长春胺缓释微丸与普通片,采用HPLC测定血药浓度,流动相0.02 mol·L-1磷酸二氢钾-乙腈(70∶30,用磷酸调节p H2.3),检测波长268 nm,比较各制剂的药动学参数。结果:长春胺缓释微丸与普通片在Beagle犬血浆中Cmax分别为(1 147.40±554.50),(1 506.10±327.44)μg·L-1;Tmax分别为(2.38±0.25),(1.63±0.25)h;MRT分别为(6.75±2.44),(3.19±0.73)h;AUC0-t分别为(4 766.76±1 740.26),(3 906.81±686.53)μg·h·L-1。长春胺缓释微丸较普通片的相对生物利用度122%,体内外相关性良好。结论:与普通片相比,长春胺缓释微丸在Beagle犬体内吸收较慢,平均滞留时间为普通片的2倍以上,生物利用度显著提高,说明该处方可实现药物在胃肠道中非p H依赖性释放。Objective： To prepare vincamine sustained-release pellets and analyze its pharmacokinetics in Beagle dogs for providing an reference for non-pH-dependent release of sustained-release formulations of vincamine. Method： Vincamine sustained-released pellets were prepared by fluidized bed with self-made tartaric acid pills core. Beagle dogs were randomly assigned to receive sustained-release pellets and common tablets with dosage of 150 mg, then a crossover trial was conducted one week later. HPLC was employed to determine plasma drug concentrations to compare pharmacokinetic parameters of each formulation, mobile phase was 0.02 mol ·L^-1 potassium dihydrogen phosphate-acetonitrile （70：30） by adjusting pH 2.3 with phosphoric acid, detection wavelength was 268 nm. Result： Pharmacokinetic parameters of sustained-release pellets and common tablets were asfollows： CmaxOf（1 147.40±554.50）, （1 506.10±327.44） μg·L^-1; Tmax Of （2.38±0.25）, （1.63±0.25） h; MRTof （6.75 ±2.44）, （3.19±0.73） h; AUCo-t of （4 766.76±1740.26）, （3 906.81 ±686.53） μg ·h · L^-1, respectively. Relative bioavailability of sustained-release pellets to common tablets was 122%. Dissolution test indicated that sustained-release pellets had good in in vivo and in vitro correlation. Conclusion： Compared with common tablets, vincamine sustained-release pellets show slower absorption in Beagle dogs, the average residence time is two times more than the former, relative bioavailability has also been significantly improved, indicating that this formulation can achieve non-pH-dependent release in the gastrointestinal tract.

关 键 词：长春胺 pH依赖性 缓释微丸 BEAGLE犬 药代动力学 

分 类 号：R945[医药卫生—微生物与生化药学] R283.6[医药卫生—药剂学]