Studies on the Metabolic Fate of Recombinant Human Erythropoietin(SNB-5001). III. Whole body Autoradiography, Foeto-placental Transfer and Excretion into Milk in Rats after Administration of 125I-SNB-5001.

Abstract

Distribution, accumulation, foeto-placental transfer and excretion of 125I-SNB-5001 into the milk were studied after intravenous (iv) or subcutaneous (sc) administration at a dose of 50 U/kg to male, pregnant and lactating rats, respectively. 1. After single iv administration to male rats, high level radioactivity was distributed rapidly in thyroid, blood, lymph, kidney, liver, bone marrow and lung and thereafter the radioactivities in most tissues, except thyroid and skin, disappeared rapidly as revealed by whole body autoradiography. After sc administration, the radioactivity was slowly distributed in the tissues at a low level, but distribution patterns were similar to those after iv administration. Distribution of radioactivity in brain and spinal cord was extremely low. 2. After repeated iv and sc administration to male rats for 7 days, distribution patterns of radioactivity were not changed compared with those after single administration. Accumulation of radioactivity in the tissues was scarcely observed except in thyroid and skin. 3. After iv administration to pregnant rats (19th day of gestation), a very small amount of radioactivity was distributed in fetal tissues except thyroid and gastric contents. TCA-insoluble radioactivity in fetus was about 30% at the early times after administration, indicating that most of the radioactivity was free 125I and 125I-compounds of low molecular weight. These results suggest that SNB-5001 is scarcely transfered into the fetus. 4. The radioactivity in the milk was increased gradually and reached the maximum of the higher level than that in maternal plasma at 6hr after iv administration to lactating rats. Afterwards, the radioactivity in milk disappeared rapidly similar to that in plasma, however, the ratio of TCA-insoluble radioactivity in milk was increased with time.