Comparison between morning and evening single dose administration of fluvastatin in hypercholesterolemic male albino rats

ABSTRACT

The concepts of chronobiology, circadian rhythm, chronopharmaology, homeostasis and chronotherapy are taken into account to approach the optimal drug therapy, in which the timing of drug administration plays an important role. Dyslipidemia is a primary, major risk factor and may be a prerequiste for coronary artery disease [CAD], occurring before other major risk factors come into play. Lipid-altering drug treatment, targeted to patients at high risk for cardiovascular disease [CVD], has been shown [in clinical trials] to reduce the incidence of first and recurrent CVI] events. The statins represent drugs of first choice for treatment of hypercholesterolemia. The aim of the present study is to determine the proper time of administration of the drug to achieve the best benefits for the hypercholesterolemic patients. The experiments were carried out on thirty two male albino rats that were divided into four equal groups; control normocholesterolemic, hypercholesterolemic non-treated, hypercholesterolemic treated in the morning with fluvastatin [8 mg/kg for 21 days] and hypercholesterolemic treated in the evening with fluvastatin [8 mg/kg for 2! days]. The present study demonstrated that administration of a single dose of fluvastatin [8 mg/kg/day for 21 days], whether given in the morning or in the evening for hvpercholesterolemic rats, significantly decreased serum total cholesterol levels in comparison with non-treated hypercholesterolemic animals. Also, fluvastatin treatment whether given in the morning or in the evening produced a significant increasing effect on high density lipoprotein serum level in comparison with the non-treated hypercholesterolemic animals. On the other hand, the level of low density lipoprotein in the evening treated hypercholesterolemic rats was siginficantly decreased, while, the morning treatment with fluvastatin showed an insignificant decreasing effect. Also, fluvastatin treatment, whether given in the morning or in the evening produced insignificant effect on serum triglycerides level in comparison with non-treated animals. Significant increase in the activity of glutathione peroxidase in serum was observed in the evening treated group in comparison with non-treated hypercholesterolemic animals, while, the morning treatment with fluvastatin showed insignificant increasing effect on glutathione peroxidase activity. Fluvastatin treatment whether given in the morning or in the evening showed nonsignificant decreasing effect on lipid peroxides content in serum in comparison with non-treated animals. It is concluded from the present data that therapeutic efficiency of fluvastatin is best obtained when the drug was administered in the evening rather than in the morning