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.