Tissue Distribution And Metabolism In Rat Of An Ethynesulphonamide With Filaricidal Activity

XENOBIOTICA(1997)

引用 3|浏览8
暂无评分
摘要
1. The tissue distribution and metabolism of a new filaricidal agent P903 (N-[(2-phenylethynyl)sulfonyl]morpholine) were studied in rat.2. After s.c. administration of C-14 and C-13 P903, the T-max in the blood was observed on day 2. Elimination was slow and > 95% was bound to protein. Radioactivity was distributed in the whole organism but particularly in erythrocytes and the lymphatic channel. Four days later, > 60% of the radioactivity was excreted in urine and faeces at equal amounts and 15% remained at the injection point.3. In all biological fluids tested no P903 was found but only its metabolites.4. One principal metabolite, the N-[(2-phenyloxo-2-ethane) sulphonyl] morpholine or oxosulphonamide was identified in blood, urine and faeces as compared with the reference compound by GC/MS and NMR. This latter molecule was detected following hydrolysis by hydrochloric acid but not with beta glucuronidase/sulphatase.5. Unconjugated and conjugated oxosulphonamide represented > 85% of the radioactivity al all times tested in blood bur only 38 and 35% respectively of urinary and faecal radioactivity on day 1 after the administration of the labelled drug.6. Thus, P903 is rapidly converted to a reactive metabolite, probably an oxirene, which is then conjugated with endogenous components to form conjugated oxosulphonamide and an unknown metabolite. The role of this reactive metabolite in antifilarial activity seems to be very important in understanding the mechanism of action of P903.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要