新抗炎症薬4-Ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone(M73101)の代謝(第4報)血中濃度および消化管吸収

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Drug disposition of 4-Ethoxy-2-methyl-5-morpholino-3 (2H)-pyridazinone (M73101) was studied in mice, rats, rabbits, and dogs. Following intravenous administration of 20 mg/kg, the plasma concentration of unchanged M73101 was decreased according to first-order elimination with the rate characteristic for each animal. The biological half-lives were 25.3,40.7,55.0,67.2 and 80.1 min in mice, rabbits, dogs, male and female rats, respectively. The distribution volumes in the animals were approximately 600 ml/kg. On the other hand, after oral administration, the plasma concentration of unchanged M73101 or radioactivity reached a peak at 30 min in mice and dogs, and at 60-120 min in rats and rabbits. The levels of unchanged M73101 within the early period in mice and rats were 43.2,41.5 and 49.1μg/ml in rats and 96.9,93.3 and 74.3μg/ml in mice at 5,15 and 30 min after administration, respectively. These differences were confirmed from the fact that the residual contents in the gastrointestinal tract were 64.1,59.5 and 52.1% of the dose administered in rats and 40.5,28.0 and 22.8% in mice at the same period. In case of direct administration into the stomach or intestine, 21.6% of the dose administered was absorbed in rats and 40.6% in mice from stomach within 30 min, and from intestine the drug was absorbed almost completely within 15 min in both species. It was concluded that M73101 administered orally was rapidly absorbed through the gastrointestinal tract and then excreted after the biotransformation, in the metabolic rate characteristic for each species.
社団法人日本薬学会の論文
1980-01-25

新抗炎症薬4-Ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone(M73101)の代謝(第4報)血中濃度および消化管吸収

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