Metabolic Fate of Clonidine. (I): Absorption, Distribution and Excretion in Rats, Dogs and Monkeys after Subcutaneous Administration of Clonidine.

Abstract

After a single subcutaneous administration of 14C-clonidine at a dose of 1 mg/kg (principally) to rats, dogs and a monkey, the absorption, distribution and excretion of radioactivity were investigated. 1. In the male rats, the radioactivity level in plasma reached a maximum (Cmax) at 2 hr and then declined with half-lives of 7.1 hr up to 24 hr and 37 hr thereafter. The plasma levels were dose-proportional at the dosing range of 0.25 to 1 mg/kg. No marked difference was observed between the males and females in the plasma level. Most tissues showed higher radioactivity levels than that observed in the plasma, especially high levels were seen in the mandibular gland, kidney, liver and stomach. The elimination from tissues was more rapid than that in the plasma except the aorta and thyroid gland until 24 hr. High radioactivity was also found in the gastro-intestinal contents, some exocrine glands and nasal cavity as revealed by the whole body autoradiograms. Urinary and fecal excretions within 168 hr were 69.5 and 28.4% of the dose, respectively. Biliary excretion accounted for 33.2% of the dose within 48 hr. Entero-hepatic circulation was partly observed. In the females, urinary excretion was slightly higher than that in the males. 2. In the male dogs, the Cmax was 6 times higher and the elimination of second phase was slower than those in the male rats. Within 480 hr, 87.0 and 10.2% of the dose were excreted in urine and feces, respectively. 3. In the male monkey, the radioactivity level in plasma and urinary and fecal excretions were similar to those in dogs.