Effects of alcohol and fluvastatin on lipid metabolism and hepatic function.
OBJECTIVE
To determine the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combined with moderate alcohol consumption on lipid profiles and hepatic function in patients with primary hypercholesterolemia.


METHODS
Randomized, placebo-controlled, crossover study.


METHODS
Lipid clinic of a university hospital.


METHODS
31 patients with primary hypercholesterolemia (low-density lipoprotein cholesterol levels > or = 4.2 mmol/L) who had previously received a lipid-lowering diet.


METHODS
After a dietary baseline period, 26 patients were randomly assigned 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 or 2) fluvastatin added to orange juice alone. After a 6-week washout period, the two groups crossed over.


METHODS
Plasma fluvastatin levels, lipid levels, and clinical variables were determined at the end of each treatment period.


RESULTS
Six patients left the study 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/m2) completed the study. Fluvastatin, alone and combined with alcohol, resulted in similar decreases in levels of total cholesterol (22% and 23%, respectively; P < 0.001 when compared with baseline), low-density lipoprotein cholesterol (28% and 29%, respectively; P < 0.001 compared 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 resulted 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) and in a greater time to maximum concentration (187.5 +/- 16.6 min compared with 130.9 +/- 7.0 min) than fluvastatin alone. Terminal half-life tended to increase. No important adverse clinical effects were observed.


CONCLUSIONS
Six weeks of daily, moderate alcohol consumption influenced the metabolism of fluvastatin but did not interfere with its lipid-lowering efficacy and had no adverse effects.
Smit
J W
JW
Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
Wijnne
H J
HJ
Schobben
F
F
Sitsen
A
A
De Bruin
T W
TW
Erkelens
D W
DW
D000328:Adult; D000428:Alcohol Drinking; D008076:Cholesterol, HDL / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects; D018592:Cross-Over Studies; D005229:Fatty Acids, Monounsaturated / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014280:Triglycerides; D000077340:Fluvastatin