Metabolism, distribution, and excretion of recombinant human thrombopoietin in mice

摘要

To study the metabolism, distribution, and excretion profiles of recombinant human thrombopoietin (rhTPO) in mice. ~(125)I-rhTPO was prepared by iodogen method anddetermined by size exclusive HPLC (SHPLC) or trichloroacetic acid (TCA) precipitation analysis. Radioactive-purity of ~(125)I-rhTPO was 96.9 %+-1.5 % (n = 3). ~(125)I- rhTPO maintained the biological activities both in-vitro and in-vivo. SHPLC analysis after sc 1 ug / mouse (345kBq / mouse) showed that there were two smaller molecular weight ~(125)I-degradation metabolites (~(125)I-MI and ~(125)I-MII) other than parent drug in serum and urine. ~(125)I-MI was detected both in serum and urine, and ~(125)I-MII was mainly found in urine. The maximal concentration was detected at 2 h after injection. The terminal T_(1/2) was 10.8 h. TCA precipitable radioactivity in tissue showed that the radioactivity in bone marrow was rather high. The highest level was found in urinary system. The lowest level was found in brain. 87.1 % +-6.1 % of injected dose was excreted through urine within 24 h.Total radioactivity does not represent the concentration of parent drug. The terminal T_(1/2) of rhTPO was much longer than that of other peptides. TCA precipitable radioactivity in target tissue was rather high. The main excretion route of rhTPO was urinary system.