1996 Volume 11 Issue 5 Pages 451-462
In order to clalify the species difference in metabolism of MCI-186, the identification of metabolites, urinary excretion rates of unchanged MCI-186 and its metabolites, and in vitro metabolism were investigated in rats, dogs and human.
1. Main metabolites of MCI-186 were sulfate and glucuronide of MCI-186 in all species. In the urine of rats and dogs, excretion rates of sulfate were higher than those of glucuronide, however in the urine of human, excretion rate of glucuronide was higher than that of sulfate, therefore species difference was observed in urinary excretion.
2. Urinary excretion was the main excretion route in all species. Excretion rates of the unchanged MCI-186 to urine were less than 3 % of dose. In dogs and human, urinary excretion can be mostly explained by excretion of unchanged MCI-186, and its sulfate and glucuronide. However in rats, unknown metabolites were present at higher rates of 20 ?? 27% of the urinary radioactivities. And sex difference in urinary excretion was not observed mostly in rats.
3. Activities of formation of MCI-186 sulfate were higher than those of MCI-186 glucuronide at in vitro metabolism of MCI-186 with liver S9 of rats and dogs. And both activities were higher in male rats than in female rats.
