Disposition of rhIGF-I. (3). Plasma level, distribution and excretion of 125I-rhIGF-I after repeated subcutaneous administration to rats.

125I-rhIGF-I was administered subcutaneously to rats at the dose of 1 mg/kg for 7 consecutive days. After seventh subcut aneous administration of 125I-rhIGF-I, the plasma levels of total and trichloroacetic acid (TCA)precipitable radioactivity declined more slowly than those after a single administration. However, it might be caused by an endogenous proteins which had incorporated a free 125I and low molecular weight fragments of 125I-rhIGF-I and the plasma levels of rhIGF-I itself were thought not to be changed after repeated administration. Except the thyroid, the permeability of rhIGF-I to tissues did not change, and no accumulation of 125I-rhIGF-I in any particular tissue was observed after repeated administration. During repeat ed administration, the excretion of radioactivity in urine and feces was almost similar to that after a single administration, and 80% and 9 % of the administered dose was excreted within 168 hours after the last dosing to urine and feces, respectively. Most of radioactivity in t he urine consisted of free 125I which indicates that 125I-rhIGF-I was well metabolized. Thus, it appears that 125I-rhIGF-I does not accumulate in tissue.