Circadian variation of the hypocholesterolemic effect of K13.004 in rats

The hypocholesterolemic effect in rats of the new lipid-lowering agent K13.004 was dependent on the time of day of its application. This dependence was shifted together with the time of peak activity of hepatic cholesterol synthesis (CS) when the feeding time of the animals was changed. This compound considerably reduced serum cholesterol only if given before the peak of hepatic CS, whereas application afterwards was ineffective. Our finding suggests that this hypolipidemic compound lowers serum cholesterol by inhibition of hepatic CS. Drugs acting in such a way should be administered prior to the maximum of hepatic sterol synthesis.