Jwa. Smit et al., EFFECTS OF ALCOHOL-CONSUMPTION ON PHARMACOKINETICS, EFFICACY, AND SAFETY OF FLUVASTATIN, The American journal of cardiology, 76(2), 1995, pp. 89-96
Alcohol consumption is known to have beneficial effects on cardiac mor
tality, probably by increasing high density lipoprotein cholesterol (H
DL-C). Alcohol also increases triglycerides and, in some studies, tota
l 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) reduct
ase inhibitors. Consequently, 2 studies have been carried out to deter
mine the effects of alcohol consumption on the pharmacokinetics and ef
ficacy of the HMG-CoA reductase inhibitor fluvastatin. Firstly, the ef
fects of acute alcohol consumption on a single, oral 40 mg dose of flu
vastatin were examined in a reference-controlled, randomized, crossove
r study in 10 healthy volunteers. Measurements were made after ingesti
on of 70 g of ethanol diluted to 20% with lemonade and, following a 7-
day period, after ingestion of lemonade alone (reference). The half-li
fe (t(l/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 refer
ence 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)-Al. Triglyceride level
s increased with alcohol, probably due to impaired fatty acid oxidatio
n. Surprisingly, total cholesterol and LDL-C fell significantly, possi
bly 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 phar
macokinetics and lipid-lowering capacity was conducted 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 t
o 20% with lemonade, or with lemonade alone (reference). After a 6-wee
k washout period, the 2 groups crossed over for a second 6-week treatm
ent period. Measurements were made at the end of each treatment period
. In the 20 patients who completed the study, no serious adverse event
s occurred. Alcohol did have some effect on fluvastatin pharmacokineti
c 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 re
ference and alcohol. However, these pharmacokinetic effects did not co
rrelate with differences in lipid parameters. Neither reference nor al
cohol showed significant changes in HDL-C or triglyceride levels, but
significant decreases in total cholesterol, LDL-C, and apo B were obse
rved; these decreases did not differ significantly between reference a
nd alcohol. In conclusion, alcohol consumption has no effect on the ef
ficacy and safety of fluvastatin treatment in patients with primary hy
percholesterolemia.