Effects of alcohol consumption on pharmacokinetics, efficacy, and safety of fluvastatin

doi:10.1016/S0002-9149(05)80026-8

The American Journal of Cardiology

Volume 76, Issues 1–2, Supplement 1, 13 July 1995, Pages 89A-96A

https://doi.org/10.1016/S0002-9149(05)80026-8 Get rights and content

Abstract

Alcohol consumption is known to have beneficial effects on cardiac mortality, probably by increasing high density lipoprotein cholesterol (HDL-C). Alcohol also increases triglycerides and, in some studies, total cholesterol and low density lipoprotein cholesterol (LDL-C). Nothing is known, however, of the effects of alcohol on the pharmacokinetics and efficacy of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Consequently, 2 studies have been carried out to determine the effects of alcohol consumption on the pharmacokinetics and efficacy of the HMG-CoA reductase inhibitor fluvastatin. Firstly, the effects of acute alcohol consumption on a single, oral 40 mg dose of fluvastatin were examined in a reference-controlled, randomized, crossover study in 10 healthy volunteers. Measurements were made after ingestion of 70 g of ethanol diluted to 20% with lemonade and, following a 7-day period, after ingestion of lemonade alone (reference). The half-life (t_1/2) of a single dose of fluvastatin was significantly reduced by acute alcohol consumption compared with reference, whereas the area under the time—concentration curve (AUC), peak concentration (C_max), and time to peak concentration (t_max) did not differ from the reference group. The lipid profile, measured 8 hr after administration, did not differ significantly from baseline in the reference group, apart from a slight reduction in apolipoprotein (apo)-AI. Triglyceride levels increased with alcohol, probably due to impaired fatty acid oxidation. Surprisingly, total cholesterol and LDL-C fell significantly, possibly due to altered pharmacokinetics, as reflected by the lower t_1/2. To assess the long-term clinical implications of these findings, a 6-week study into the effects of alcohol consumption on fluvastatin pharmacokinetics and lipid-lowering capacity was concluded in 26 patients with primary hypercholesterolemia (LDL-C 4.2 mmol/liter after dietary baseline period). Patients were randomized to 6-week treatment with 40 mg/day of fluvastatin, combined with either 20 g of alcohol diluted to 20% with lemonade, or with lemonade alone (reference). After a 6-week washout period, the 2 groups crossed over for a second 6-week treatment period. Measurements were made at the end of each treatment period. In the 20 patients who completed the study, no serious adverse events occurred. Alcohol did have some effect on fluvastatin pharmacokinetic parameters; a tendency to lengthen t_1/2 and to increase AUC and t_max compared with reference, without a difference in C_max between reference and alcohol. However, these pharmacokinetic effects did not correlate with differences in lipid parameters. Neither reference nor alcohol showed significant changes in HDL-C or triglyceride levels, but significant decreases in total cholesterol, LDL-C, and apo B were observed; these decreases did not differ significantly between reference and alcohol. In conclusion, alcohol consumption has no effect on the efficacy and safety of fluvastatin treatment in patients with primary hypercholesterolemia.

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Effects of alcohol consumption on pharmacokinetics, efficacy, and safety of fluvastatin

Abstract

J Lipid Res

J Lipid Res

Atherosclerosis

Atherosclerosis

Am Heart J

J Chron Dis

Lancet

J Lipid Res

J Lipid Res

J Lipid Res

Metabolism

Atherosclerosis

Metabolism

J Chromatogr

Pharmacol Biochem Behav

Regulation of hepatic cholesterol metabolism in man

Ann Med

Familial hypercholesterolemia

Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog

Mevinolin stimulates receptor mediated clearance of low density lipoprotein from plasma in familial hypercholesterolaemia heterozygotes

Trans Ass Am Phys

HMG-CoA reductase inhibitors for treatment of hypercholesterolaemia

N Engl J Med

Mevinolin and colestipol stimulate receptor mediated clearance of low density lipoprotein from plasma in familial hypercholesterolaemiaheterozygotes

Suppression of apolipoprotein B production during treatment of cholesterol ester storage disease with lovastatin. Implications for regulation of apolipoprotein B synthesis

J Clin Invest

HMG CoA reductase inhibitors as lipid lowering agents five years experience with lovastatin and appraisal of simvastatin and pravastatin

Q J Med

Comparison of different HMG-CoA reductase inhibitors

Eur J Clin Pharmacol

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolaemia

Arch Intern Med

Long term efficacy and safety of simvastatin in patients with familial hypercholesterolaemia

Diab Nut Melab

Efficacy and long-term adverse effect pattern of lovastatin

Am J Cardiol

Long term clinical tolerance of lovastatin and simvastatin

Cardiology

Extended clinical safety profile of lovastatin

Am J Cardiol

Wine, garlic and CHD in seven countries

Lancet

Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine

Lancet

Alcoholic beverages and myocardial infarction in young men

Am J Epidemiol