Studies on the metabolic fate of S-3460. (II). Absorption, distribution and excretion after repeated subcutaneous administration to rats.

Abstract

The absorption, distribution and excretion of S-3460 in male rats were studied following 7- or 28-day period of daily subcutaneous administration of 3H-S-3460 or 14C-S-3460 at 0.5 mg/kg. 1. The concentrations of radioactivity in plasma and blood 24 hr after daily administration rose with increasing of dosing times, and its concentration after the 28 th dose was 4.3 and 17 times higher than that after a single dose, respectively. Thus, it seems that the accumulation in plasma is low while that in blood is significantly high. Tissue concentration of radioactivity also rose and reached plateau levels by the 28 th dose in most tissues except for the blood, kidney and spleen. 2. The concentrations of radioactivity in the plasma, blood and most tissues after repeated administration of 3H-S-3460 were slightly higher than those after a single dose, but the disappearances were significantly slow. In some tissues, the levels after 3H-S-3460 administration differed from those after 14C-S-3460 administration. This may have been due to detachment of 3H from the 1, 2 position of 3H-S-3460. Tissue levels of radioactivity in female rats were lower than those in male rats and transfer of radioactivity with blood cell was also low. 3. Excretion of radioactivity into the urine and feces was almost constant during repeated administration and that after the 7 th or 28 th dose was similar to that after a single dose. Most of the radioactivity was excreted via the feces in both male and female rats.