新抗炎症薬4-Ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone(M73101)の代謝(第3報)ラットにおける生体内動態およびイヌにおける腎からの排泄

抄録

The fate of ³H-labeled 4-ethoxy-2-methyl-5-morpholino-3 (2H)-pyridazinone (³H-M73101) in rats and the excretion of M73101 from dog kidney were studied. When ³H-M73101 was given orally to rats, it was rapidly absorbed from the gastro-intestinal tract and widely distributed throughout the tissues. Particularly, higher radioactivity was detected in the stomach, kidney and liver. Plasma concentration reached maximum at 1 hr after administration and maintained that level for 3 hr ; thereafter, radioactivity rapidly decreased. The time courses of radioactivity in many tissues were similar to those in plasma. Autoradiographic results were in good accord with those described above. Radioactivity was found also in the inflammed site and carboxymethyl cellulose (CMC) pouch of rats at 1 hr after administration. At 6 hr, radioactivity in the skin and muscle in contact with the CMC pouch was higher than that at normal sites. Excretions into the urine and feces within 24 hr were 68.6% and 18.9% of the dose, respectively. About 10% of the dose was excreted into the bile within 24 hr, in which parent compound and 6 metabolites were detected. When the excreted bile was administered into the duodenum, 23% of the dose was excreted again into the bile. From the result of the experiment using a renal clearance method in dogs, it was found that more than 95% of M73101 was reabsorbed from the renal tubule by passive transport. The relationship between the fate and the pharmacological activity of M73101 is also discussed.