ANALYSIS - PAGE 3 b:
Because grapefruit juice is also metabolized by CYP3A4, the combination of grapefruit juice and simvastatin should cause results similar to that of the simvastatin and itraconazole combination. High concentrations of the simvastatin in the blood would result as less is metabolized.
In comparison, itraconazole has a minor effect on the metabolism of pravastatin, which is considered not significant. The small difference may have been caused by minor experimental error. It can therefore be concluded that pravastatin is metabolized by enzymes other than CYP3A4 that were not inhibited by itraconazole. Because CYP3A4 comprises the majority of the microsomes, the amount of other enzymes is lower, causing the metabolism of pravastatin to be lower than that of simvastatin.
Fenofibrate and niacin had insignificant effects on the metabolism of simvastatin. They therefore have no effect on CYP3A4 and can be taken with other medication that is metabolized by that enzyme. However, they significantly decreased the percent of pravastatin that was metabolized. Because of the interaction, it is likely that fenofibrate and niacin act as inhibitors to the enzyme responsible for pravastatin metabolism.
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