Studies on the Metabolic Fate of HSR-803 (I): The Absorption, Distribution and Excretion in Rats and Dogs after Single Administration
1994 Volume 9 Issue 3 Pages 308-326
Details
1994 Volume 9 Issue 3 Pages 308-326
The absorption, distribution and excretion of N-[p-[2-(Dimethylamino)-ethoxy]benzyl]veratramide hydrochloride (HSR-803) were investigated in rats and dogs following single administration of 14C-labelled compound.
1. Blood and serum radioactivity reached the Cmax at 0.5 to 1 hr after single oral administration of 14C-HSR-803 to rats and dogs, and then declined with half-lives of 3.42, 10.30 hr for whole blood and 3.78, 10.12 hr for serum, respectively. The site of absorption in rats was the entire intestine, particularly the duodenum.
2. Radioactivity level was high in tissues such as the small intestine, stomach, kidney and liver of rats after oral administration of 14C-HSR-803. In the central nervous system, the concentration was low. Elimination from each tissue was rapid. Radioactivity in the stomach wall in rats was high after intravenous administration of 14C-HSR-803.
3. When 14C-HSR-803 was administered orally, urinary and fecal excretions were 63.6 and 35.7% of the dose for rats, and 46.7 and 50.9% of the dose for dogs, as determined within 168 hrs. In rats and dogs, 68.1 and 79.3% of the dose were excreted into bile after oral dosing, respectively. In rats, enterohepatic circulation was observed.
4. In vitro protein binding to human, rat and dog serum was 95.5, 79.6 and 57.5% at the concentration range of 0.2-10.0 μg/ml, respectively.
