Metabolic fate of KRN8601 : Plasma level, distribution, metabolism and excretion of 125I-KRN8601 after a single intravenous administration to rats

The plasma levels, tissue distribution, metabolism and excretion of 125I-KRN8601 after a single intravenous administration were investigated in male and female rats. After an intravenous administration of 125I-KRN8601 at a dose of 5μg/kg, plasma levels of total, trichloroacetic acid (TCA) precipitable and immunoreactive radioactivity decreased in biphasic manner. More than 90% of radioactivity in plasma was retained to be TCA precipitable and immunoreactive for one hour following the administration. There was no difference in the half-life, distribution volume and AUC between male and female rats. In the case of increasing of dose level, no differences in the half-life and distribution volume were observed, while AUC increased proportionally to administered dose level. Ten minutes after intravenous administration, high levels of radioactivity were observed in the plasma, adrenals, blood, kidney, thyroid, liver and bone marrow. Radioactivities in most tissues were below the plasma level and decreased in parallel with that in any time interval. Low radioactivity levels were detected in the brain, eyes, skeletal muscle, thymus and adipose tissue. These results were in good agreement with those of whole body autoradiograms. Distribution profiles of radioactivity in female did not differ from those in male rats with the exception of genital organs. TCA precipitable radioactivities were shown at high level in the kidney, liver and spleen and in plasma as well, but a low level was detected in the stomach and small intestine. Within 72 hours after intravenous administration, most of the administered radioacitvity was excreted in urine in the form of free iodine. Biliary excretion of rdioactivity was also observed, mostly as compounds of low molecular weight.