论文部分内容阅读
采用液相色谱-串联质谱法分别测定人和Beagle犬口服阿托伐他汀钙片后血浆中的阿托伐他汀(1)及其活性代谢物,包括邻位羟基化物(2)和对位羟基化物(3),计算并对比人和Beagle犬血浆中1、2、3的药动学参数。结果显示,药物在人体内主要以原型1的形式存在,检测不到代谢物3;而在Beagle犬体内主要以代谢物2的形式存在,另检测到原型药物占约30%,代谢物3约占5%。原型药物1在人体内的消除半衰期约为Beagle犬的3倍,而清除率仅约为Beagle犬的65%。可见,人与犬口服药物的药动学存在显著的种属间差异,Beagle犬对原型药物的代谢速度和程度均显著高于人体。
Plasma samples of atorvastatin (1) and its active metabolites, including ortho-hydroxylates (2) and para-hydroxy groups (2), were determined by liquid chromatography-tandem mass spectrometry after oral administration of atorvastatin calcium tablets Compounds (3) were calculated and compared in human and Beagle dog plasma 1, 2, 3 pharmacokinetic parameters. The results showed that the drug mainly exists in the form of the prototype 1 in the human body, and the metabolite 3 can not be detected. In the Beagle dog, the metabolite 2 mainly exists, and the prototype drug accounts for about 30%, the metabolite 3 about 5%. Prototype drug 1 has a half-life in humans that is about 3 times lower than in Beagle dogs and a clearance rate of only about 65% in Beagle dogs. Visible, human and canine oral pharmacokinetics there are significant differences between species, Beagle dogs on the prototype drug metabolism rate and degree were significantly higher than the human body.