Studies on the metabolic fate of M17055,a novel diuretic (2):tissue distribution and transfer of radioactivity into fetus and milk in rat after a single intravenous administrtion of [~(14)C]M17055

摘要

Tissue distribution and the transfer of radioactivity into the fetus or milk were studied following a single intravenous administration of [~(14)C]M17055 to rats at a dose of 0.3mg/kg.1.Tissue levels of radioactivity in male rats showed maximum level in most tissues at 5 minutes after addministration.The concentrctions in kidney nd liver showed respectively 11.7 and 8.1 fold greater levels than that in plasma,while tha levels in other tissues were lower than those in plasma.Then the levels of radioactivity in most tissues decreased to undetectable levels within 168hours after administration.2.Although higher kidney/plasma ratio of radioactivity was observed in female rats,the distribution of radioactivity in female rats showed similar pattern when compared with that in male rats.3.After administration to pregnant rats on 12th and 19th day of gestation,a little radioactivity was transferred into the fetus and eliminated slowly in the rats on 19th day of gestation.Although temporary rising of radioactivity was observed in the intestine and its contents of the fetus,the radioactivity decreased to undetectable level in newborn rats showed similar pattern compared with that in non-pregnant female rts,which suggested that the influence of pregnancy on the distributiion seems to have minimal effect in female rat.4.The level of radioactivity in the milk reached a miximum level (63mg eq./mL)at 2 hours and exceeded the plasmal level within 2 approx 12 hours after administration.Then the radioactivity decreased rapidly and reached lower level than that in plasma at 48 hours after administration.