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

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t_max和t_1/2分别为0.7～1.0 h和3.5～4.3 h；3个剂量组的AUC_0-∞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，AUC_0-∞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 t_max and t^1/2 of ATPT in dogs were 0.7-1.0 h and 3.5-4.3 h，respectively.While the areas under the curve (AUC_0-∞) 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 c_max/AUC_0-∞ 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.