1990 Volume 5 Issue 6 Pages 795-817
The absorption, distribution and excretion of radioactivity following a single or multiple subcutaneous administration of 14C-MF in rats were studied.
1. When 14C-MF was administered at 0.5 or 1 mg/kg, a dose independent values of Cmax (26 ?? 30ng equiv./ml in male and 31 ?? 32ng equiv./ml in female) and of Tmax(ca.2hr in male and 3 ?? 4hr in female) were observed in rats. However, T1/2 and AUC changed depending on the dose. Cmax in rabbits was lower than rats (11ng equiv./ml). In rats, the elimination of whole blood radioactivity was slower than that of plasma.
2. Plasma protein binding of 14C-MF in vitro was more than 99% in rats, rabbits and humans and those in vivo were more than 94% in rats and rabbits. Distribution of 14C-MF into blood cell in vitro was 0 % in rats, 30% in rabbits and 4 ?? 7 % in humans.
3. The highest radioactivity level was found in the liver and followed by the kidney, intestine and fatty tissues. Radioactivities in tissues other than blood, liver and kidney disappeared with almost similar rate as that of plasma and decreased to undetectable level at 168 hr after administration.
4. Radioactivity was excreted predominantly into feces via bile in both animal species. Approximately 20% of the biliary radioactivity was reabsorbed from the intestinal tract in male rats.
5. After multiple administration, radioactivity levels in the plasma and most tissues reached nearly steady-state after 4 ?? 8 times dosing. However, levels in blood increased with dosing time, and it disappeared very slowly after the last dose. Most of the radioactivities in blood cell and liver after multiple administration were recovered from the cytoplasmic lipid and protein fractions.
6. Excretion profile was not altered by multiple administration.
