Abstract
The distribution, accumulation and urinary or biliary excretion of SK-827 were investigated in male rats after single or repeated intravenous administrations of 125I-SK-827.
1. The blood trichloroacetic acid insoluble (TCA-insoluble) radioactivity after a single intravenous injection of 125I-SK-827 at a dose of 5×10-3 PNAU (p-nitroaniline unit) /kg decreased rapidly within 1 hr, but thereafter in more gradual rate. At 5 min ?? 1 hr after injection, the TCA-insoluble radioactivity in the liver, adrenal, spleen, kidney and bone marrow were higher than that in the blood. At 5 min after injection, more than 90% of administered radioactivity was concentrated in the liver. The TCA-insoluble radioactivity in these tissues decreased rapidly within 1 hr, and the elimination was similar to that in the blood thereafter. Distribution profiles of radioactivity after a single constant rate intravenous infusion did not differ from those after intravenous injection.
2. TCA-insoluble radioactivity in the liver, kidney and spleen at 1, 3 and 24 hr after 4-day repeated intravenous injections of 125I-SK-827 at the dose of 5×10-3 PNAU/kg were 2 ?? 10 times higher than those observed after a single dose but the TCA-insoluble radioactivity in these tissues were almost constant from 4-day to 7-day repeated dosing.
3. Within 24 hr after a single intravenous injection of 125I-SK-827 at a dose of 5×10-3 PNAU/kg, more than 90% of administered radioactivity was excreted into urine. However, urinary excretion of TCA-insoluble radioactivity was only 1% of administered dose within 3 hr after injection.
4. Within 48 hr after a single intravenous injection of 125I-SK-827 at a dose of 5×10-3 PNAU/kg, about 20% of administered radioactivity was excreted into bile. However, biliary excretion of TCA-insoluble radioactivity was only 3% of administered dose within 3 hr after injection.
