Magyar K
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
Pol J Pharmacol Pharm. 1987 Mar-Apr;39(2):107-12.
EGYT-475 (N-benzyl-piperazine-picolinyl fumarate; Trelibet) metabolism was compared in rats, dogs and man. In the rat 7 urinary metabolites of EGYT-475 were found, and 4 were identified as: N-picolinyl-piperazine (EGYT-1354) (30%), picolinic acid (28.5%), hippuric acid (53%) and N-benzylpiperazine (EGYPT-2760) (3.7%). The results show that debenzylation is the main route of EGYT-475 metabolism in the rat. By this route EGYT-2760, the active EGYT-475 metabolite, is further metabolized. In the dog the main metabolic pathway is hydrolysis, and because of that the formed EGYT-2760 is not metabolized further and its urinary content exceeds 50%. In man, similarly as in the rat, debenzylation is the preferred route of EGYT-475 metabolism. These results explain much higher toxicity of EGYT-475 in dogs than in rats and man.
对EGYT - 475（富马酸N - 苄基 - 哌嗪 - 吡啶基酯；Trelibet）在大鼠、狗和人体中的代谢情况进行了比较。在大鼠体内发现了7种EGYT - 475的尿液代谢产物，其中4种已被鉴定为：N - 吡啶基 - 哌嗪（EGYT - 1354）（30%）、吡啶甲酸（28.5%）、马尿酸（53%）和N - 苄基哌嗪（EGYT - 2760）（3.7%）。结果表明，脱苄基作用是EGYT - 475在大鼠体内的主要代谢途径。通过该途径，活性EGYT - 475代谢产物EGYT - 2760会进一步代谢。在狗体内，主要代谢途径是水解作用，因此生成的EGYT - 2760不会进一步代谢，其尿液中的含量超过50%。在人体中，与大鼠一样，脱苄基作用是EGYT - 475代谢的首选途径。这些结果解释了EGYT - 475对狗的毒性远高于对大鼠和人体的毒性。
