Most of the statins (lovastatin, simvastatin, atorvas-tatin, and cerivastatin) are metabolized by the cytochro-mal P450 3A4 system of intestines and liver to more water-soluble metabolites that are excreted in both the bile and urine. Drugs that inhibit P450 3A4, such as itraconazole, cyclosporine, and erythromycin, can vastly (10fold) increase plasma statin levels and thus increase the risk of toxicity. Unexpectedly, grapefruit juice can inhibit intestinal metabolism of the statins and can result in an 8- to 10-fold increase in simvastatin serum levels. Since fluvastatin is metabolized by cytochrome P450 2C9, which is also responsible for metabolism of warfarin, warfarin toxicity may be increased if these drugs are simultaneously given. Grapefruit juice should obviously not be consumed within several hours of statin administration. Drugs that induce the P450 3A4 system, such as barbiturates, can accelerate statin metabolism and suppress statin blood levels.
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