Effects of alcohol consumption on pharmacokinetics, efficacy, and safety of fluvastatin.
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 (t1/2) 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 (Cmax), and time to peak concentration (tmax) 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 t1/2.(ABSTRACT TRUNCATED AT 250 WORDS)
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 / Q000378:metabolism / Q000503:physiopathology*; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D018592:Cross-Over Studies; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006207:Half-Life; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D007211:Indoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012449:Safety; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014280:Triglycerides; D000431:Ethanol; D000077340:Fluvastatin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases