Seville Orange Interactions

Seville (bitter) orange contains the same furanocoumarins as grapefruit, including bergamottin and 6',7'-dihydroxybergamottin, which irreversibly inhibit intestinal CYP3A4. A landmark crossover study showed Seville orange juice raised felodipine AUC by 76%, comparable to grapefruit, and atorvastatin shares the same CYP3A4 metabolic pathway, raising the risk of statin-induced myopathy.

Seville orange juice contains furanocoumarins that reduce enterocyte CYP3A4 expression by approximately 40%, although a controlled human study found no significant change in cyclosporine AUC, likely because cyclosporine disposition also depends on intestinal P-glycoprotein, which Seville orange does not inhibit as strongly as grapefruit.