Triton‐induced hyperlipidemia in rats as an animal model for screening hypolipidemic drugs

Abstract

Abstract We describe a screening test for hypolipidemic agents in which compounds are administered orally to fasted rats after a single intravenous injection of 225 mg Triton WR‐1339/kg and serum cholesterol and triglycerides are measured 43 hr post‐Triton. Conditions for the screen were established by studying interrelationships between serum cholesterol, triglycerides and Triton levels during the post‐Triton period and the effects of Triton dose, route of administration and fasting on serum lipid levels and drug hypocholesterolemic activity. The test detects compounds which inhibit lipid biosynthesis or stimulate lipid catabolism. Several drugs with different mechanisms of action which are hypolipidemic in man, including nicotinic acid, D ‐thyroxine, triparanol, nafoxidine HCl and clofibrate are active in this system. Results with standard hypolipidemic agents are reproducible and conform well to performance levels of the screen predicted from statistical analysis.