Hypocholesterolemic Activity of Raloxifene (LY139481): Pharmacological Characterization as a Selective Estrogen Receptor Modulator

After once-daily oral dosing in ovariectomized rats, raloxifene (LY139481) hydrochloride produced dose- and time-depen-dent reductions in serum cholesterol and high-density lipopro-tein-cholesterol. Paired-feeding studies demonstrated that ef-fects of raloxifene on serum lipids were not secondary to effects on food consumption. Maximal reductions in serum cholesterol occurred within 4 days of raloxifene administration or sooner, depending on the administered dose. The ED50 for 50 % reduction in serum cholesterol by raloxifene was 0.13 6 0.04 mg/kg/day (mean 6 S.E.M., n 5 17); maximal cholesterol reduction by raloxifene (68%) was significantly less than that produced by estrogen (17a-ethinylestradiol; 89%) after 4 to 7 days of daily dosing. Dose-response curves for cholesterol lowering by raloxifene were generated in the presence of vary