Abstract
In dogs, no significant difference in the reduction of serum cholesterol was observed among three dosing regimens of pravastatin: once in the morning (3 mg/kg), once in the evening (3 mg/kg), and twice-daily (1.5 mg/kg × 2) for 21 days. In rabbits, pravastatin was administered at a dose of 50 mg/kg once-daily given in the evening or 25 mg/kg twice-daily for 14 days; the respective serum and liver cholesterol levels were decreased by 41% and 7% in the once-daily dosing and by 51% and 11% in the twice-daily dosing. The amount of low density lipoprotein (LDL) receptor protein was increased 1.2-1.3-fold (P < 0.05) by both treatments, and no significant difference was noted between these treatment regimens. In addition, there was no significant difference in the extent of up-regulated LDL receptor protein between once-daily dosing in the evening and once-daily dosing in the morning. In the experiments with rabbit hepatocytes, the up-regulated LDL receptor activity induced by preincubation with pravastatin was retained even 24 hr after the removal of pravastatin. These results suggest that the comparable efficacy of pravastatin between once and twice-daily treatment could be explained by retention of up-regulated LDL receptor activity for more than 24 hr in vitro and in vivo.
