Since simvastatin is metabolised by the cytochrome P450 system, a potential for drug interactions exists. Elevated HMG-CoA reductase inhibitory activity has been observed when simvastatin was administered concurrently with cyclosporin, possibly increasing the risk of myopathy and subsequent rhabdomyolysis which are associated with simvastatin use. Simvastatin has also been shown to potentiate the effects of warfarin. A rapid decrease in cholesterol levels is observed within the first 2 weeks of simvastatin treatment Tolerance to these effects has not been observed. Simvastatin can be administered as a single dose, preferably in the evening. Simvastatin is well absorbed from the gastrointestinal tract but is highly extracted by the liver and only 7% of the dose reaches the general circulation intact. The peak inhibition of HMG-CoA reductase activity occurs within 2 to 4 hours. Increasing the dose of simvastatin from 5 to 120mg increases the pharmacological activity in a linear fashion. The several metabolites tend to remain within the liver and the intestines (via biliary excretion). Some gastrointestinal reabsorption of metabolites may occur. Simvastatin is eliminated mainly in the faeces due to biliary excretion but only a small percentage of the dose is found in the stool in the form of the parent compound or simvastatin acid. Since simvastatin is metabolised by the cytochrome P450 system, a potential for drug interactions exists. Elevated HMG-CoA reductase inhibitory activity has been observed when simvastatin was administered concurrently with cyclosporin, possibly increasing the risk of myopathy and subsequent rhabdomyolysis which are associated with simvastatin use. Simvastatin has also been shown to potentiate the effects of warfarin. A rapid decrease in cholesterol levels is observed within the first 2 weeks of simvastatin treatment. Tolerance to these effects has not been observed. Simvastatin can be administered as a single dose, preferably in the evening.