Absorption, Distribution and Excretion of OPB-2045 following a Single Subcutaneous Administration to Rats.

Abstract

Examination was made of the absorption, distribution and excretion of radioactivity in SpragueDawly rats following a single subcutaneous administration of 14C-labeled OPB-2045 at 1 mg/kg, and the following results were obtained: 1. Serum concentrations of radioactivity were maximum (Cmax) of 0.032-0.033 μg eq./ml at 1 hr after administration in male and female rats. Radioactivity half-life in serum was 77.0 hr as determined at 48 hr to 168 hr postdosing in male and female rats. The area under the serum concentration-time curve (AUC0→∞) was 0.75 to 0.78 μg eq.·hr/ml. Radioactivity in blood cells accounted for 31.9-77.9% of total radioactivity in the blood. Radioactivity in the blood exceeded that in the serum. AUC0→∞ in the blood was 1.5 to 2 times that of the serum. 2. Radioactivity was highest in the pituitary gland, followed by the thyroid, adrenal glands, lungs and kidneys in male rats 1 hr postdosing. In tissues, it was 10 to 26 times higher than in the blood. At 8 and 24 hr postdosing, radioactivity in adrenal glands was extremely high, and 100 to 200 times that in the blood. At 72 and 168 hr postdosing, radioactivity was high in the adrenal and pituitary glands and kidneys. Its tissue distribution in female rats was essentially the same as in male rats. 3. Urinary and fecal excretion of radioactivity was 17.2-20.8% and 68.4-71.2% of the administered doses, respectively, with 9.1-9.3% remaining in the carcass at 168 hr postdosing. 4. Biliary and urinary excretion of radioactivity at 24 hr postdosing accounted for 34.1% and 14.2% the administered doses, respectively, in male rats whose bile ducts had been cannulated.