Grapefruit Juice and Some Oral Drugs: A Bitter Combination

Grapefruit juice has been found to interact with many oral drugs when taken concomitantly. Studies have shown that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4)- an important enzyme involved in drug metabolism- via mechanism-based inactivation. Drug elimination is therefore prevented, and as a result, the bioavailability of many orally administered drugs is substantially increased when the patient ingests grapefruit juice. The grapefruit-drug interaction may result in severe side effects, ranging from hypotension to fatal cardiac arrhythmias. The active ingredients in grapefruit juice are substances of the coumarin family, primarily 6'7'-dihydroxybergamottin (DHB), a compound that inhibits CYP3A4 by causing irreversible inactivation of the enzyme. A flavenoid, naringenin, is also though to play a minor role. Furthermore, the effects of grapefruit juice can last over 24 hours since last consumption. Because many drugs, including felodipine, terfenadine, cyclosporine, and saquinavir, are metabolized by CYP3A4, it is very important to be aware of the potential side effects if grapefruit juice is consumed while patients are on medications that are metabolized by this enzyme.