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 cholesterol when given in a single evening dose. Absorption and rate of bioavailability may be affected when administered with food, but the effect of mealtime dosing on efficacy and safety has not been evaluated. This multicenter, double-blind, placebo-controlled crossover study was performed in 44 patients with primary hypercholesterolemia. Patients received 20 mg of fluvastatin with the evening meal and placebo at bedtime for 6 weeks, followed by 12 weeks of placebo at mealtime and fluvastatin at bedtime (group 1). Group 2 received the opposite treatment schedule, and group 3 received placebo at mealtime and at bedtime for 12 weeks before receiving 20 mg of fluvastatin at bedtime instead of placebo for the final 6 weeks. Fluvastatin with the evening meal resulted in a marginally lower peak serum concentration (p < 0.1) and a significantly delayed time to peak concentration compared with bedtime dosing, but there were no statistically significant differences in the extent of bioavailability. At the end of the first 6 weeks of treatment, similar reductions in low-density lipoprotein (LDL) cholesterol were obtained whether fluvastatin was given at mealtime (- 21.8%; p < 0.001) or 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 lipoprotein (HDL) ratio (p < 0.001) irrespective of the time of dosing. In conclusion, fluvastatin had a similar tolerability, safety, and efficacy, 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.