Abstract
Beneficial effects of HMG-CoA reductase inhibitors, such as simvastatin have been attributed to lipid lowering and cholesterol-independent mechanisms, for example a reduction of monocyte adhesion to endothelium. However, little 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 monocytes isolated from healthy volunteers or mildly hypercholesterolemic patients 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 unaltered and the observed effects did not correlate with systemic concentrations of the pro-drug nor the active drug concentration in the peripheral circulation. In conclusion, the transient increase in adhesiveness of monocytes may be due to direct and/or enterohepatic metabolites of simvastatin, demonstrating the necessity of drug metabolism for exerting the beneficial effects of long-term treatment.
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