Distribution of recombinant human erythropoietin following multiple intravenous administration and effects of age on the distribution in rats.

Multiple administration of 125I-recombinant human erythropoietin (125I-rh-EPO) did not cause an accumulation of intact EPO in tissue. The gel filtration profile of tissue from rats given multiple doses of 125I-rh-EPO was very similar to that for rats given single doses of 125I-rh-EPO, suggesting that intact rh-EPO (CAS 11096-26-7) does not accumulate. Pretreatment of rats with non-labeled rh-EPO did not cause a change in the ratio of metabolites to intact rh-EPO, as judged by the gel filtration data. This indicates that multiple administrations do not cause a change in metabolic pathways in the tissues. The tissue to plasma concentration ratio (t/p ratio) of rh-EPO in the target organ, i.e., the bone marrow and spleen, decreased with increase of age; the spleen showed a marked decrease in t/p ratio as compared to the bone marrow. On the other hand, t/p ratios in the kidney and liver did not change for periods of 4 to 31 weeks.