Metabolic Fate of YM175—Distribution and Excretion of Radioactivity after Intravenous Administration of 14C-YM175 to Rats—

The tissue distribution and excretion of radioactivity were investigated after a single intravenous administration of 0.3 mg/kg of 14C-YM175 to rats. 1. YM175, labelled with 14C, concentrated into the bones a target organ, rapidly after intravenous administration to rats, and remained there for a long period. Though radioactivity level in the kidney was almost equal to that in the bone at 5 min after dosing, the concentration in other tissues/organs was lower than the plasma concentration; the lowest in the brain. Radioactivity disappeared slowly from the spleen, liver, bone marrow, rib and humerus, whereas in other tissues, radioactivity disappeared relatively rapidly. 2. Humerus and rib radioactivity levels decreased bi-exponentially, with t1/2α alues of 4.8 and 8.9 days, and t1/2β values 331 and 214 days, respectively. 3. The autoradiography of humerus revealed high levels of radioactivity in the metaphysis followed by the diaphysis and epiphysis, but radioactivity was not detected in the marrow cavity. Radioactivity in the humerus remained at the site of initial localization, and was not found in the portion that grew subsequently. Humerus radioactivity concentrations decreased on decalcification to 0.2-0.6% of that prior to decalcification. 4. Within 168 hr after dosing, 64.5 and 2.5% of the dosed radioactivity was excreted in the urine and feces, respectively. At the end of this period 32.9% of the dosed radioactivity was remained in the carcass, hence total recovery was 99.9%. In bile-duct cannulated rats, 0.8 and 57.0% of the dosed radioactivity was excreted within 48 hr in the bile and urine, respectively.