Pharmacokinetics and hypolipidemic activity of clofibrate-nicotinic acid combinations in rats

Abstract

Male albino rats were given various oral doses of clofibrate and nicotinic acid. both alone and in combination, daily for 1 week. In normal animals, the combination of drugs produced greater decreases in serum lipids, notably triglycerides, than equimolar doses of either drug alone. Synergistic decreases in serum triglycerides were observed in rats rendered hypertriglyceridemic with fructose and treated simultaneously with both drugs. The peak level of serum nicotinic acid was higher and the area under the serum nicotinic acid concentration-time curve (AUC) was 59 per cent greater when nicotinic acid was given with clofibric acid (CPIB) than when given alone. Pretreatment for 1 week with nicotinic acid slightly increased the apparent volume of distribution and the elimination half-life of intravenously injected CPIB. The presence of nicotinic acid in rat serum did not affect the protein binding of CPIB. The results show that the combined hypolipidemic effect of clofibrate and nicotinic acid in rats is accompanied by changes in the pharmacokinetics of the drugs, the most pronounced being a decrease in the rate of elimination of nicotinic acid.