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Recently some researchers have shown that furanocoumarins rather than flavonoids are the ingredients causing the various drug interactions.Grapefruit juice has also been reported to increase both the bioavailability of some benzodiazepines, (such as diazepam) and greatly slow the rate of metabolization. An easy way to tell if a medication may be affected by grapefruit juice is by researching whether another known CYP3A4 inhibitor drug is already contraindicated with the active drug of the medication in question. Examples of such known CYP3A4 inhibitors include cisapride (Propulsid),[citation needed] erythromycin, itraconazole (Sporanox), ketoconazole (Nizoral),and mibefradil (Posicor). The flavonoid existing in highest concentration in grapefruit juice is naringin, which in humans is metabolised to naringenin. Other flavonoids exist in grapefruit juice in lower concentrations as well. Orange juice does not contain naringin in as high a concentration, instead containing hesperetin. It is sometimes recommended as a substitute. Juice of limes and Seville oranges can also inhibit drug metabolism, however, as can apple juice with some drugs.
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