Beneficial effects of HMG-CoA reductase inhibitors, such as simvastatin hav
e been attributed to lipid lowering and cholesterol-independent mechanisms,
for example a reduction of monocyte adhesion to endothelium. However, litt
le is known about acute effects of statin intake. In an attempt to test for
short-term effects of drug intake, we found that the adhesion of blood mon
ocytes isolated from healthy volunteers or mildly hypercholesterolemic pati
ents was increased after intake of simvastatin but not placebo at 0.5 h and
declined to baseline levels at 3 h. Blood cholesterol levels were unaltere
d and the observed effects did not correlate with systemic concentrations o
f the pro-drug nor the active drug concentration in the peripheral circulat
ion. In conclusion, the transient increase in adhesiveness of monocytes may
be due to direct and/or enterohepatic metabolites of simvastatin, demonstr
ating the necessity of drug metabolism for exerting the beneficial effects
of long-term treatment, (C) 2001 Elsevier Science Ireland Ltd. All rights r
eserved.