Studies on the metabolic fate of M17055,a novel diuretic(1):plasma concentration and excretion of radioactivity in rat and dog after a single intravenous administration of [~(14)C]M17005

摘要

The plasma level and excretion of radioactivity were stuided following a single intravenous administration of [~(14)C]M17055 to male and female rats,and a female dog.1.After a single intravenous administration to male and female rats at a dose of 0.3mg/kg,plasma levels of radioactivity declined triphasically reaching at 48hr the levels lower than /1000 or those observed at one minute after administration.Calculated CLtot,T_(1/2#beta#) and T_(1/2#gamma#)did not differ between male and female rats.But T_(1/2#alpha#)of female rats showed lower value than that of male rats.2.After a single intravenous administration to male rats at doses of 0.1,1 and 3mg/kg,plasma levels of radioactivity declined in similar manner with that at a dose of 0.3,g/kg.lthough calculated CLtot tends to decline at 1 and 3 mg/kg,the T_(1/2#gamma#)showed similar value at the dose range of 0.1-3mg/kg.3.Plasma level of radioactivity in a female dog declined triphasically reaching at 48hr the levels 100 fold lower than those observed at 5 minutes after a single intravenous administration at a dose of 1mg/kg.Thereafter,the level of radioactivity declined more slowly when compared with rats.4.Cumulative urinary and fecal excretions after a single intravenous administration to a female dog accounted for over 90precent after administration.Total excetion of radioactivity within 168 hours accounted for 97.33precnet of the administered dose.5.Cumulative urinary and fecal excretions after a single intravenous administration to a female dog accounted for over 90precent after administration.Total excretion of radioactivity within 168 hours accounted for 97.33precnet of the administered does.6.Biliary excretion of radioactivity after a single intravenous administration to bile-duct cannulated male rats accounted for 64.12precent of the dose.About 67 precent of the excreted radioactivity in bile was re-absorbed in male rats.7.The renal clearance of radioactivity after administration in male and female rats decreased and showed same level when treated with probenecid,which suggested that the sez difference of the urinary excretion may be caused by the active secretary mechainsm.