抗高血压候选药物ATPT在比格犬体内的药代动力学  

Pharmacokinetics of a novel antihypertension candidate ATPT in Beagle dogs

作　　者：冯冬[1] 孙建国[1] 朱胤慈[1] 彭英[1] 祁欢欢[1] 张凤逸[1] 王广基[1] 

机构地区：[1]中国药科大学江苏省药物代谢动力学重点实验室,南京210009

出　　处：《中国药科大学学报》2013年第2期151-155,共5页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2009ZX09304-001;No.2009ZX09102-036);中央高校基本科研业务费专项资金资助项目(No.JKP2009007)~~

摘　　要：采用LC-MS/MS方法对ATPT在比格犬体内的药代动力学特征进行了研究。结果表明,比格犬单次灌胃给予ATPT混悬液后,ATPT在比格犬体内的药代动力学行为符合二房室模型特征;ATPT在比格犬体内吸收迅速,并且达峰后消除迅速,3个剂量组(7.5,15,30 mg/kg)的tmax和t1/2分别为0.7～1.0 h和3.5～4.3 h;3个剂量组的AUC0-∞分别为(5 465.9±1 748.7)、(7 846.2±3 547.4)和(15 490.9±8 292.4)ng.h/mL,AUC0-∞与剂量间呈良好的线性关系,呈线性动力学过程;经过剂量校正,求得ATPT在比格犬体内的绝对生物利用度分别为39.7%、28.5%和28.1%。An LC-MS/MS method was used for the evaluation of a novel antihypertension candidate pharmacokinetics of ATPT in Beagle dogs.After ig administration of 7.5,15 and 30 mg/kg ATPT,the determined tmax and t1/2 of ATPT in dogs were 0.7-1.0 h and 3.5-4.3 h,respectively.While the areas under the curve（AUC0-∞） were（5 465.9±1 748.7）,（7 846.2±3 547.4） and（15 490.9±8 292.4） ng ·h/mL at three doses,respectively.Good linearity was observed between cmax/AUC0-∞ and dose（R20.98） after a single ig administration of 7.5,15 and 30 mg/kg in dogs.After adjustment of dose,the absolute bioavailabilities of ATPT in dogs were 39.7%,28.5% and 28.1%,respectively.It presented a linear pharmacokinetics for ATPT in Beagle dogs within the dose range of the study.

关 键 词：ATPT 抗高血压药物 AT1受体拮抗剂 LC-MS MS 药代动力学 

分 类 号：R969.1[医药卫生—药理学]