Comparative study on the in vivo and in vitro antilipolytic effects of etofibrate, nicotinic acid and clofibrate in the rat

The release of both glycerol and free fatty acids (FFA) into a medium by epididymal fat pad pieces from fed rats incubated in Krebs Ringer bicarbonate-albumin buffer supplemented or not with epinephrine decreased more in the presence of etofibrate than in the presence of equimolecular doses of nicotinic acid or clofibrate. The first drug was the only one to stimulate the rate of fatty acid re-esterification when incubations were done under basal conditions. By 3 h after their acute oral administration all three drugs decreased plasma FFA levels, although the effect from etofibrate was largest, the drugs enhanced or decreased plasma glycerol levels depending on both the dose and the time after treatment. Plasma triglycerides also decreased at 3 h after oral drug administration, and this effect was similar with etofibrate and nicotinic acid but less with clofibrate. With the exception of a decrease at 7 h after the highest dose (1.2 mmol/kg) of either etofibrate or nicotinic acid (but not clofibrate), plasma cholesterol levels remained stable at 7 h after the respective treatments. Thus, the hypocholesterolemic effect of these drugs seems secondary to their hypotriglyceridemic effect, which would be a consequence of their respective antilipolytic actions, and follows an efficiency sequence of etofibrate, nicotinic acid and clofibrate.