Effects of F2833 on cholesterol metabolism in the genetically hyperlipidemic rat

The effects of the new hypolipidemic agent, F2833 or (chloro 2' (1-1') biph enyl-4)-2 propanol-2, on cholesterol metabolism were studied in genetically hyperlipidemic rats (RICO). Cholesterolemia decreased after 2 days of trea tment to 60% of its initial value (1.20 +/- 0.10 g/l vs. 1.99 +/- 0.08, P < 0.001) and then stabilised within 10 days. This hypocholesterolemic action was effective for as long as 3 months. Concerning the different classes of lipoproteins, a significant drop was observed in HDL thigh density lipopro teins) (25%, 0.49 <plus/minus> 0.02 g/l vs. 0.66 +/- 0.007, P < 0.01) and p articularly in LDL (low density lipoproteins) (70%, 0.30 <plus/minus> 0.04 g/l vs. 0.92 +/- 0.05, P < 0.001). Whole body cholesterol showed a higher f ractional catabolic rate (0.25 <plus/minus> 0.02 vs. 0.17 +/- 0.005 day(-1) P < 0.01) together with an increased cholesterol synthesis (60 <plus/minus > 5 vs. 36 +/- 4 mg/day, P < 0.01). LDL kinetics showed that the decrease i n these lipoproteins is essentially caused by an increase in the fractional catabolic rate (10.6 <plus/minus> 0.1%/h vs. 5.2 +/- 0.1%/h, P < 0.001) an d by a lesser decrease in the LDL production rate. This cholesterol metabol ic profile created by treatment suggests an effect through stimulation of c holesterol output (biliary cholesterol elimination or cholesterol transform ation into bile acids). (C) 2001 Published by Elsevier Science B.V.