Grapefruit CYP3A4 interactions

In addition to CYP3A4, enterocyte efflux transport proteins such as P-gp, and enterocyte uptake proteins, such as OATPs also appear to be involved in grapefruit rug interactions (24,72). The activity of P-gp has been reported to be altered by GFJ and orange juice in in vitro experiments (73,74), whereas the clinical relevance currently seems unclear, as demonstrated by inconsistent results from human clinical trials (22,75 77). 

Fukuda K, Ohta T, Oshima Y, Ohashi N, Yoshikawa M, Yamazoe Y. Specific CYP3A4 inhibitors in grapefruit juice furocoumarin dimmers as components of drug interaction. Pharmacogenetics 1997 7 391-396. 

For several phenolics from citrus, such as eriocitrin, poncirin, and sinapic acid and anthocyanins, which occur in red grapefruit varieties and blood oranges, no specific drug interactions and also no interactions with CYP3A4 and P-gp are reported. 

Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John s wort, and certain anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone)... 

Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20-mg single-dose exposure (AUC) by 312%. Other CYP inhibitors—Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. 

Because grapefruit juice is known to inhibit CYP3A4-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, grapefruit juice should not be taken during treatment with oral amiodarone (see Precautions Drug interactions )... 

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