Dosing Time‐Dependent Effect of Raloxifene on Plasma Fibrinogen Concentration in Ovariectomized Rats

The chronopharmacological effect of raloxifene, a selective estrogen‐receptor modulator, was evaluated by repeated dosing of ovariectomized rats. Bilateral ovariectomy or sham operation was performed at age 12 wks, and animals were kept in rooms with a 12 h light‐12 h dark cycle. Raloxifene (3 mg/kg, once daily for 10 wks) or vehicle was given repeatedly at either 2 h after lights‐on (2 HALO) or 14 h after lights‐on (14 HALO). Plasma fibrinogen concentration at the end of the study was reduced by the drug, and the reduction was significantly prominent in rats in whom the drug was dosed at 2 HALO rather than 14 HALO. Femur bone density decreased, and urinary excretion of deoxypyridinoline, an index of bone resorption capacity of osteoclasts, increased in ovariectomized animals at the end of the study. Treatment with raloxifene ameliorated these changes in a dosing time‐independent manner. Serum calcium, ALT, and total protein concentrations at the end of the study also did not differ acccording to treatmen...