Disposition of Marograstim (KW-2228) (1) : Plasma concentration, distribution, metabolism and excretion of ¹²⁵I-KW-2228 after intravenous or subcutaneous administration to rats

Abstract

Plasma concentration, distribution, metabolism and excretion of ¹²⁵I-KW-2228, a mutant of human granulocyte colony stimulating factor, were studied in rats after single intravenous or subcutaneous administration.
1. After intravenous administration of ¹²⁵I-KW-2228, total radioactivity and trichroloacetic acid(TCA)-insoluble radioactivity in the plasma were eliminated biexponentially. TCA-insoluble radioactivity showed a rapid elimination as compared with total radioactivity. Maximum concentrations of total and TCA-insoluble radioactivity were reached at 2hr after subcutaneous administration. After that, TCA-insoluble radioactivity was eliminated more rapidly than total radioactivity in a case of intravenous administration. The results of SD S-PAGE suggested that most of antibody-bound able radioactivity in the plasma were unchanged KW-2228 in both administration routes.
2. TCA-insoluble radioactivity was distributed to the kidney at the highest concentration, suggesting that the kidney might play the major role in metabolism and elimination of ¹²⁵I-KW-2228. Other tissues showed a difference in the distribution pattern of ¹²⁵I-KW-2228 after intravenous and subcutaneous administrations. In the bone marrow, the target organ of KW-2228, the elimination of radioactivity was slower after subcutaneous administration, which was thought to contribute to higher WBC increasing effect. A high level of radioactivity was observed in the thyroid gland, stomach and skin, which might be related to the ¹²⁵I released from ¹²⁵I-KW-2228.
3. The major excretion route of ¹²⁵I-KW-2228 was urine and there was no difference between administration routes. Most of radioactivity in the urine consisted of low molecular weight metabolites or free ¹²⁵I.