FLUVASTATIN ADMINISTRATION AT BEDTIME VERSUS WITH THE EVENING MEAL - A MULTICENTER COMPARISON OF BIOAVAILABILITY, SAFETY, AND EFFICACY

Fluvastatin is a totally synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is effective in reducing cholest erol when given in a single evening dose. Absorption and rate of bioav ailability may be affected when administered with food, but the effect of mealtime dosing on efficacy and safety has not been evaluated. Thi s multicenter, double-blind, placebo-controlled crossover study was pe rformed in 44 patients with primary hypercholesterolemia. Patients rec eived 20 mg of fluvastatin with the evening meal and placebo at bedtim e for 6 weeks, followed by 12 weeks of placebo at mealtime and fluvast atin at bedtime (group 1). Group 2 received the opposite treatment sch edule, and group 3 received placebo at mealtime and at bedtime for 12 weeks before receiving 20 mg of fluvastatin at bedtime instead of plac ebo for the final 6 weeks. Fluvastatin with the evening meal resulted in a marginally lower peak serum concentration (p < 0.1) and a signifi cantly delayed time to peak concentration compared with bedtime dosing , but there were no statistically significant differences in the exten t of bioavailability. At the end of the first 6 weeks of treatment, si milar reductions in low-density lipoprotein (LDL) cholesterol were obt ained whether fluvastatin was given at mealtime (- 21.8%; p < 0.001) o r at bedtime (- 23.9%; p < 0.001). After crossover of groups 1 and 2, the results remained constant. With fluvastatin, there were comparable reductions in total cholesterol (p < 0.001) and in LDL:high-density l ipoprotein (HDL) ratio (p < 0.001) irrespective of the time of dosing. In conclusion, fluvastatin had a similar tolerability, safety, and ef ficacy, whether given with the evening meal or at bedtime. There were no serious adverse events nor changes in physical examination findings or laboratory values attributable to treatment.