ABSTRACT
Dyslipidemia is a major risk factor for coronary heart disease [CHD], and its management is important in preventing the occurrence of cardiovascular events. Lipid-altering drug treatment, targeted to patients at high risk for cardiovascular disease, has been shown [in clinical trials] to reduce the incidence of first and recurrent CHD events. Statins are used widely for the treatment of dyslipidemia. They act through reversible competitive inhibition of the hepatic 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis. The early use of statin in management of dyslipidemia recommended their morning administration. However, this strategy should be re-evaluated in light of reports showing that the biosynthesis of cholesterol exhibits diurnal periodicity with nocturnal increase in the level of cholesterol precursors. The experiments were performed on forty male albino rats divided after estimation of basic lipid profile into four equal groups, each composed of 10 animals: control normocholesterolemic, hypercholesterolemic non-treated, hypercholesterolemic treated with morning fluvastatin [8mg/kg, for 12[th] weeks] and hypercholesterolemic treated with evening fluvastatin [8mg/kg for 12[th] weeks]. Lipid profile was estimated at the end of the 4[th], 8[th], 12[th] and 16[th] weeks for all animals using spectrophotometeric assay kits and the results were expressed in mg/dl. Both morning and evening treatment with fluvastatin significantly reduced blood cholesterol level and low-density lipoprotein. Significant increase of plasma high density lipoprotein level was observed in evening treated group in comparison with non-treated hypercholesterolemic animals. Interestingly, all these beneficial effects of fluvastatin treatment were more significant when administered in the evening rather than in the morning pattern of treatment. On the other hand, fluvastatin treatment whether given in the morning or in the evening for hypercholesterolemic animals, produced no significant effect on plasma triglyceride level and total lipid level in comparison with non-treated hypercholesterolemic animals. It is concluded that therapeutic efficiency of fluvastatin is best obtained when the drug was administered in the evening rather than in the morning. This most likely occurred due to the circadian rhythm of cholesterol biosynthesis. This chronotherapeutic pattern of fluvastatin recommends its night administration to ensure introduction of the drug at the proper timing thus achieving the best therapeutic effect