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抗高血压候选药物ATPT在比格犬体内的药代动力学

冯冬, 孙建国, 朱胤慈, 彭英, 祁欢欢, 张凤逸, 王广基

冯冬, 孙建国, 朱胤慈, 彭英, 祁欢欢, 张凤逸, 王广基. 抗高血压候选药物ATPT在比格犬体内的药代动力学[J]. 中国药科大学学报, 2013, 44(2): 151-155. DOI: 10.11665/j.issn.1000-5048.20130210
引用本文: 冯冬, 孙建国, 朱胤慈, 彭英, 祁欢欢, 张凤逸, 王广基. 抗高血压候选药物ATPT在比格犬体内的药代动力学[J]. 中国药科大学学报, 2013, 44(2): 151-155. DOI: 10.11665/j.issn.1000-5048.20130210
FENG Dong, SUN Jianguo, ZHU Yinci, PENG Ying, QI Huanhuan, ZHANG Fengyi, WANG Guangji. Pharmacokinetics of a novel antihypertension candidate ATPT in Beagle dogs[J]. Journal of China Pharmaceutical University, 2013, 44(2): 151-155. DOI: 10.11665/j.issn.1000-5048.20130210
Citation: FENG Dong, SUN Jianguo, ZHU Yinci, PENG Ying, QI Huanhuan, ZHANG Fengyi, WANG Guangji. Pharmacokinetics of a novel antihypertension candidate ATPT in Beagle dogs[J]. Journal of China Pharmaceutical University, 2013, 44(2): 151-155. DOI: 10.11665/j.issn.1000-5048.20130210

抗高血压候选药物ATPT在比格犬体内的药代动力学

基金项目: 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)

Pharmacokinetics of a novel antihypertension candidate ATPT in Beagle dogs

  • 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tmaxt1/2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%。
    Abstract: 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 (R2>0.98 ) 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.
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  • 刊出日期:  2013-04-24

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