EFFECTS OF ALCOHOL AND FLUVASTATIN ON LIPID-METABOLISM AND HEPATIC-FUNCTION

Objective: To determine the effects of fluvastatin, a synthetic 3-hydr oxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combine d with moderate alcohol consumption on lipid profiles and hepatic func tion in patients with primary hypercholesterolemia. Design: Randomized , placebo-controlled, crossover study. Setting: Lipid clinic of a univ ersity hospital. Patients: 31 patients with primary hypercholesterolem ia (low-density lipoprotein cholesterol levels greater than or equal t o 4.2 mmol/L) who had previously received a lipid-lowering diet. Inter ventions: After a dietary baseline period, 26 patients were randomly a ssigned to receive 6 weeks of treatment with either 1) fluvastatin, 40 mg/d, added to 20 g of ethanol and diluted to 20% with orange juice o r 2) fluvastatin added to orange juice alone. After a 6-week washout p eriod, the two groups crossed over. Main Outcome Measures: Plasma fluv astatin levels, lipid levels, and clinical variables were determined a t the end of each treatment period. Results: Six patients left the stu dy prematurely. The remaining patients (15 men, 5 women; mean age +/- SD, 49.1 +/- 14.5 years; mean body mass index +/- SD 24.5 +/- 2.2 kg/m (2)) completed the study. Fluvastatin, alone and combined with alcohol , resulted in similar decreases in levels of total cholesterol (22% an d 23%, respectively; P < 0.001 when compared with baseline), low-densi ty lipoprotein cholesterol (28% and 29%, respectively; P < 0.001 compa red with baseline), and apolipoprotein B (17% and 20%, respectively; P < 0.001 compared with baseline). High-density lipoprotein cholesterol and triglyceride levels were not changed. Fluvastatin with alcohol re sulted in a significantly greater area under the plasma concentration curve (23.4 +/- 4.7 compared with 18.2 +/- 3.2 x 10(3) ng . min/mL) an d in a greater time to maximum concentration (187.5 +/- 16.6 min compa red with 130.9 +/- 7.0 min) than fluvastatin alone. Terminal half-life tended to increase. No important adverse clinical effects were observ ed. Conclusion: Six weeks of daily, moderate alcohol consumption influ enced the metabolism of fluvastatin but did not interfere with its lip id-lowering efficacy and had no adverse effects.