Metabolic Fate of Clonidine. (III): Absorption, Distribution and Excretion in Rats after Repeated Subcutaneous Administration of Clonidine.

Abstract

After repeated subcutaneous administration of 14C-clonidine to male rats once a day for 21 days at a dose of 1 mg/kg/day, the absorption, distribution and excretion of radioactivity were investigated. 1. No marked variation was observed in the radioactivity level of the plasma at every 24 hr after daily administration. After the final dosing, the elimination of radioactivity from the plasma after 24 hr was slower than that after single dosing. 2. The radioactivity levels in most tissues at 24 hr after daily administration achieved nearly a steady state by the 21st dosing, but the level in aorta increased cumulatively and the value was 10 times higher than that after the first dosing. After the final dosing, the elimination of radioactivity from the tissues after 24 hr was slower than that after single dosing. On the whole body autoradiograms, high radioactivity was also found in the gastro-intestinal content, some exocrine glands and nasal cavity. 3. The total excretion of radioactivity in the urine and feces during each 24 hr after daily dosing was almost constant after the 2nd dosing and 71.6 and 26.4% of the cumulative dose were excreted in the urine and feces, respectively, within 168 hr after the final dosing.