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Grapefruit juice--drug interactions: update on the most common and clinically significant.

Article Excerpt
In 1991, grapefruit juice was found to increase the oral bioavailability and effects of felodipine. (1) Since that discovery, grapefruit juice has been implicated in interactions with more than 25 medications. (2) In addition, ingestion of the whole fruit has been found to cause the same drug interactions as the juice. (3) One case report linked consumption of grapefruit juice and concurrent use of the antihistamine terfenadine (which is no longer on the market) with the death of a 29-year-old man. (4)

Here we focus on the most clinically relevant grapefruit juice--drug interactions to date. The Table lists many of these interactions from a wide variety of drug classes, including calcium channel antagonists, (1,5) HMG-CoA reductase inhibitors, (6) protease inhibitors, (7) benzodiazepines, (8) and immunosuppressants. (9,10) A review of all documented and potential interactions with grapefruit juice is beyond the scope of this overview, however.

PROPOSED MECHANISMS OF GRAPEFRUIT JUICE-DRUG INTERACTIONS

According to the current literature, there may be 3 different mechanisms that explain the effect of grapefruit juice on drug bioavailability.

Inhibition of intestinal CYP3A4. The first mechanism is the inhibition of intestinal cytochrome P-450 (CYP) 3A4 enzymes but not hepatic CYP3A4 enzymes. (2,3,11-13) Evidence for the selective inhibition of CYP3A4 in the gut is supported by the finding that grapefruit juice affects only drugs that are administered orally; it does not affect the same drugs when they are given intravenously. (11,14) Also, drugs that have a high inherent oral bioavailability are least affected...