The disposition of recombinant human erythropoietin (EPOCH) after subcutaneous administration. (2). The disposition of 125I-EPOCH after single subcutaneous administration in rats.

Abstract

We studied the absorption, distribution, excretion and metabolism of 125I-EPOCH after single subcutaneous administration to rats. 1. The levels of immunoreactive rad ioactivity reached the maximum at 8 to 12 hours after dosing and declined monoexponentially with a half-life ranging from 5.77 to 7.47 hours at the doses of 0.5, 1, 5 and 25μg/kg. The MRT of immunoreactive radioactivity after sc dosing ranged from 13.83 to 17.01 hours at any dose levels. F value (AUCsc/AUCiv), which ranged from 0.31 to 0.48, tend to increase in proportion to the administered dose. 2. Most of tissues showed the highest level of total radioactivity at 10 hour after dosing. The level of radioactivity in tissues were lower, than that of serum, except the thyroid gland whose level was the highest. They declined parallel with disappearence of the radioactivity in serum. The level of radioactivity in brain was extremely low. The elimination half-life of radioactivity from the injection site was calculated to be 9h and 1.97% of the dose still remained there at 48 hour. 3. Until 96h after sc administration of 125I-EPOCH at the dose of 1μg/kg, urinary excretions of total, the TCA-precipitable and the immunoreactive radioactivity were 75.89%, 0.35%, 0.05%, respectively. Fecal excretion of total radioactivity was 2.97%, until 96h after dosing. 4. Gel filtration of the plasma showed that the radioactivity of low molecular weight was iodo ion, and that related to radioactivity of high molecular weight appeared mainly as an unchanged 125I-EPOCH.