Metabolic fate of KRN8601: Plasma level, distribution and excretion of 125I-KRN8601 after repeated intravenous administration to rats.

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Plasma level, distribution and excretion of 125I-KRN8601 after sixth cosecutive daily intravenous administrations were examined in male rats. After sixth intravenous administration of 125I-KRN8601 at the dose of 5μg/kg/day, the plasma levels of total and trichloroacetic acid precipitable radioactivity declined more slowly than those after a single administration, whereas no difference in the plasma level profile of immunoreactive radioactivity was seen when compared to that after a single administration. Except the thyroid which showed the extremely high level of radioactivity, the concentration of radioactivity in each organ decreased with time after repeated administration, and no accumulation of 125I-KRN8601 in any particular organs or tissues was observed. Excretion of radioactivity in urine and feces was almost constant, i.e. over 70% and 4 ?? 6 % of each administered dose, respectively, during repeated administration. Finally, more than 90% or the administered radioactivity excreted in the urine and feces within 96 hours after the last dosing. All the radioactivity excreted in urine appeared to be low molecular weight compounds.
日本薬物動態学会の論文