The effect of simvastatin results from inhibition of the enzyme HMG-CoA reductase. This enzyme is significantly involved in the synthesis of cholesterol in the liver. The inhibition therefore results in an overall lower cholesterol level in the blood. Indirectly, the reduced synthesis also increases the number of receptors for LDL cholesterol in the body's cells, as a result of which LDL cholesterol in particular is more readily absorbed from the blood into the cells.
The oral bioavailability of simvastatin is only about 5%. However, this value is irrelevant in the case of simvastatin, since the drug's site of action is the liver. Thus, 100% of the given dose reaches the desired target. The highest plasma concentration is reached after about 1.5-2.5 hours. Approximately 95% of the substance is bound in the blood. The majority of the substance is broken down in the liver via the CYP3A4 and CYP3A5 enzymes and excreted in the urine (40%) and stool (60%). The elimination half-life is approximately 4 hours.
All drugs interacting with CYP3A4 may lead to increased plasma levels of simvastatin, resulting in serious side effects.