奇壬醇胃肠吸收及其缓释微丸在比格犬体内的药动学  

Absorption mechanism of kirenol and pharmacokinetic analysis of its sustained-release pellets in beagles

作　　者：何冬梅 关世侠[1] 付宏征[2] 卢舒凡[1,3] 周祥萍 

机构地区：[1]广州中医药大学中药学院,广州510006 [2]北京大学天然药物及仿生药物国家重点实验室,北京100191 [3]北京大学深圳医院,深圳518036

出　　处：《中国新药杂志》2017年第23期2788-2793,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创新"科技重大专项资助项目(2012ZX09103201-022)

摘　　要：目的:考察奇壬醇在大鼠胃肠道吸收,以及奇壬醇原料药和自制缓释微丸在比格犬体内的药动学。方法:采用大鼠体胃吸收实验以及肠外翻囊法,用HPLC法测定含量,考察奇壬醇的吸收部位及特性。将6只比格犬随机分为2组,采用单剂量双交叉实验设计分别灌胃(ig)给予奇壬醇原料药及其缓释微丸(2 mg·kg^(-1)),用LC-MS法测定血药浓度,用DAS 2.1.拟合药动学参数。结果:奇壬醇在胃肠内各部位均有吸收,但在胃的吸收速率常数Ka以及Papp显著小于各肠段(P<0.01);随着奇壬醇质量浓度的增加,奇壬醇在各肠段的吸收速率常数Ka也随之增大;药动学研究显示奇壬醇缓释微丸具有较好的缓释特性,且AUC0→t是原料药的6.56倍。结论:奇壬醇的主要吸收部位是肠段,且在各肠段吸收为被动吸收;与原料药相比,缓释微丸呈现缓释特征,且生物利用度显著提高。Objective ： To investigate the absorption characteristics of kirenol in the gastrointestinal tract ot rats, and the pharmacokinetics of kirenol stuff and homemade sustained-release pellets in Beagle dogs. Methods： The in situ closed loop method and everted gut sacs model were used to explore the absorption characteristics; A single oral dose of kirenol stuff and sustained-release pellets at a dosage of 2 mg＂ kg-I was performed according to a two-period crossover design, The concentration of kirenol was determined by LC-MS. Results： Kirenol was absorbed by both the stomach and intestine, but the absorption was better in the intestine than in the stomach （P 〈 O. 01） ; The Ka of different intestine segments increased with the increase of the concentration of Kirenol; The characteristics of plasma concentration-time curve was fitted to a two-compartment model, The AUC0_, of sustained- release pellets was 6.56 times higher, compared with stuff. Conclusion： The intestinal was the main absorption site of kirenol, and the absorption pattern suggested that kirenol was passively transported; Compared with the stuff, the kirenol sustained-release pellets showed sustained-release characteristics, and the bioavailability was significantly improved.

关 键 词：奇壬醇 胃肠吸收 缓释微丸 比格犬 药动学 

分 类 号：R945[医药卫生—微生物与生化药学]