烟酰水杨酸及其活性代谢产物在动物体内药动学研究

 目的研究烟酰水杨酸在动物体内的吸收、分布、排泄、生物利用度及血浆蛋白结合率等药动学特性。方法烟酰水杨酸生物样品的浓度采用高效液相色谱法测定。结果犬按100 mg·kg^-1剂量口服烟酰水杨酸,其药-时曲线符合二室开放模型特征,消除半衰期为0.61 h,且符合一级动力学消除。家兔按100 mg·kg^-1剂量给予烟酰水杨酸后相对生物利用度为64%。小鼠按100 mg·kg^-1剂量给烟酰水杨酸后,血浆中浓度低,心、肝、脑、肾中分布少,其代谢产物烟酸和水杨酸在血浆组织器官分布较多。烟酰水杨酸兔血浆蛋白结合率为37.3%～57.4%。尿中烟酰水杨酸浓度低,排泄以烟酸和水杨酸及其代谢产物为主。结论烟酰水杨酸吸收快,血浆蛋白结合率低,组织分布少,消除半衰期短,在血浆及肝脏中被分解成水杨酸和烟酸,主要以水杨酸和烟酸及其代谢产物经肾排泄。

Pharmacokinetics of Nicotinylsalicylic Acid and Its Active Metabolites in vivo

OBJECTIVE To study the absorption,distribution,excretion,bioavailability and protein binding of nicotinylsalicylic acid in dog,rabbit and mice.METHODS The HPLC assay was used to determine the nicotinylsalicylic acid concentrations in biological samples.RESULTS The concentration-time curve of nicotinylsalicylic acid in dogs after an ig administration of 100 mg·kg^-1 was discribed by a two-compartment open model with the elimination half-life of 0.61 h.The relative bioavailability of nicotinylsalicylic acid in rabbits was 64%.The level of nicotinylsalicylic acid was very low in mice heart,liver,brain and kidney,because it was metabolized to active nicotinic acid and salicylic acid.The protein binding rates of nicotinylsalicylic acid were in the range of 37.3%～57.4%.Nicotinylsalicylic acid at low level,and both of salicylic acid and nicotinic acid at high level were obtained in rabbit urine.CONCLUSION The absorption of nicotinylsalicylic acid is rapid,its half-life is short because it is metabolized to active nicotinic acid and salicylic acid in liver and plasma.The tissue distribution and protein binding is low.Nicotinic acid,salicylic acid and their metabolites are excreted by kidney.