Transient increase of monocyte adhesion after a single dose of simvastatin

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.