1997 Volume 12 Issue 3 Pages 173-177
The previous studies have shown that there was the species difference between rat and mouse inthe metabolic fate of KBT-3022, and that the O-demethylation of two methoxyphenyl groups of desethyl KBT-3022 (M9) was main metabolic pathway. The study of metabolism of M9 by rat liver, lung, kidney and small intestine 9, 000×g supernatant suggested that liver was the most active metabolizing organ.
In this study, we have investigated the in vitro metabolism of M9 using 9, 000×g supern atant of liver homogenates of male rats and mice in order to clarify the species difference in the metabolic fate of M9.
The metabolic activity of M9 and the O-demethylase activity of 9, 000×g supernatant of liver homogenates of rats were much higher than those of mice. The activity of demethylation of 5 methoxyphenyl group of M9 was higher than that of 4-methoxyphenyl group, both in rats and mice. However, in the demethylation of monodesmethylated M9 in rats, the activity of demethylation of 4-methoxyphenyl group was higher than that of 5-methoxyphenyl group.
These results suggest that the species difference in the demethylation of M9 by 9, 000×g supernatant of liver homogenates relates to the species difference in the metabolic fate of KBT-3022.
