Tadashi Hirata

Disposition of Marograstim (KW-2228). (2). Plasma level, distribution, metabolism and excretion of 125I-KW-2228 following multiple subcutaneous administrations of KW-2228 to rats.

Plasma concentration, distribution, metabolism and excretion of KW-2228 following multiple subcutaneous administrations for 10 days were studied in rats using 125I-labelled KW-2228 in rats, and the obtained results were compared with those after single administration. 50μg/kg/day of KW-2228 were given to rats for 9 days and 125I-KW-2228 on the 10th day only, and then concentration of radioactivity was determined. Cmax, AUC, T1/2 and Cltot calculated from TCA-insoluble radioactivity after multiple administrations did not differ from those obtained following single administration. The highest concentration of radioactivity was found in the kidney, same as observed by single administration. The distribution and elimination in other tissues, including the target organ, bone marrow, were also similar to those after single administration, indicating no cumulative effect, Most of radioactive substances were, like after single administration, excreted in urine, which were TCA-soluble and a low molecular weight metabolites such as 125I. These results show that none of plasma pharmacokinetics, distribution, metabolism and excretion differ from those obtained after single administration and that the pharmacokinetics of KW-2228 is not affected by multiple subcutaneous administration.