盐酸关附甲素在Beagle犬体内口服药代动力学和绝对生物利用度研究  

Pharmacokinetic and absolute bioavailability study of Guanfu Base A hydrochloride in Beagle dogs

作　　者：孙建国[1] 肖亚楠[1] 彭英[1] 张雪媛[1] 吴慧[1] 俞广为[1] 刘静涵[2] 吴民淑[1,3] 阿基业[1] 王广基[1] 

机构地区：[1]中国药科大学药代动力学重点实验室 [2]中国药科大学天然药物化学教研室 [3]中国药理学报,上海200031

出　　处：《中国临床药理学与治疗学》2012年第12期1378-1383,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金："十一五"重大新药创制项目资助(2009ZX09103-345);国家级大学生实践创新训练计划项目资助(J0630858;201210316068)

摘　　要：目的:采用液相色谱-质谱联用分析方法研究盐酸关附甲素在Beagle犬体内的吸收特性。方法:6只Beagle犬采用双交叉实验设计,空腹单次静脉或灌胃给予盐酸关附甲素(4mg/kg),采集不同时间点的血样,采用LC-MS法进行血浆药物浓度测定,求算相应的药代动力学参数。结果:6只Beagle犬灌胃4mg/kg盐酸关附甲素后体内过程符合二房室模型,实测的血浆药物浓度曲线下面积AUC0-48h为(18429±7281)ng·mL-1·h,最大血浆药物浓度Cmax为(1988±972)ng/mL,达峰时间tmax为(0.8±0.7)h,末端相消除半衰期t1/2为(11.2±1.6)h。与静脉注射给药相比其绝对生物利用度F为(99.0±11.2)%,拟合求得的吸收速率常数(K01)为(7.563±4.612)/h。结论:盐酸关附甲素在Bea-gle犬体内吸收迅速且完全,临床上可考虑采用口服剂型代替注射剂以便于病人用药。AIM： An LC-MS method was developed and validated for the analysis of Guanfu Base A in dog plasma to support the pharmacokinetic study.METHODS： Blood was withdrawn at different times and absolute bioavailability was studied by LC-MS at dosage of 4 mg/kg in 6 beagle dogs.RESULTS：The pharmacokinetic of Guanfu Base A in Beagle dogs fits best to two compartment model with AUC0-48 h,Cmax,tmax and half life t1/2 of（17623.9±7006.4） ng·mL-1·h,（1988±972）ng/mL,（0.8±0.7） h,and（11.2±1.6） h,respectively.Compared with i.v administration,the absolute bioavailability of Guanfu Base A was（99.0±11.2）%,with absorption rate（K01）at（7.563±4.612）/h.CONCLUSION： After oral administration,GFA can be rapidly and completely absorbed by Beagle dogs,which suggested that oral administration of Guanfu Base A could be a substitute way for anti-arrhythmic treatment.

关 键 词：盐酸关附甲素 液相色谱-质谱联用 药代动力学 BEAGLE犬 

分 类 号：R969[医药卫生—药理学]