Grapefruit and Prescription Drugs: Mix Carefully

One day in 1989, a Canadian medical scientist, a former world-class runner, was noodling around in his laboratory when he made a stunning accidental discovery, one that is still reverberating today in the world of pharmacology. His totally unexpected finding: grapefruit juice interfered with the action of an important blood pressure drug.

Dr. David Bailey, the first Canadian to run a four-minute mile, was working with a research group at the University of Western Ontario in London, Ontario, to see whether people needed to stop drinking alcohol while they were taking a drug called felodipine (Plandil), one of a class called calcium channel blockers that help lower blood pressure.

Bailey, a nondrinker, was his own guinea pig, but he hated the taste of alcohol. Orange juice wasn't enough to block the taste. So he tried double-strength grapefruit juice, and that did he trick.

Lo and behold, Bailey discovered that when he took felodipine with grapefruit juice his blood-concentration of the drug was four times as high as it should have been. In other words, a standard dose combined with grapefruit juice was four times as potent as it was without grapefruit juice. Very perplexing.

The surprising finding was first published in The Lancet, a prominent medical journal.

Reaction from both the medical community and the public was slow at first, because no one denies the health-promoting effects of grapefruit and grapefruit juice, and grapefruit seems to help people lose weight to boot.

But today, more than 30 commonly prescribed drugs carry a warning against mixing their use and grapefruits or grapefruit juice. This is not innocuous, because so many Americans have grapefruit for breakfast at a time when they also take their medications.

So why is a grapefruit a two-faced fruit? What's in a grapefruit that's not in an orange, apple or cranberry, or other juices? In 1993, the Canadian group and another from the University of Michigan homed in on an important enzyme, CYP 3A4, in the wall of the intestine. It was known that when something interferes with the breakdown of medicines by this enzyme, blood levels of a drug can rise inappropriately.

The responsible compound in a grapefruit has not been isolated. Some biochemists believe that the culprit may be a bioflavonoid, perhaps whatever it is that gives grapefruit its unique bittersweet taste. The only other fruit that shares the "grapefruit effect" appears to be Seville oranges, used primarily for making marmalade.

The "grapefruit effect" can be strong. A glass of grapefruit juice, or a half grapefruit, consumed even 24 hours before or after taking certain drugs, perhaps as long as 48 hours, can interact with certain drugs. For some people, though, this may not be so. It seems to depend on the amount of CYP 3A4 in the digestive tract, which varies greatly from person to person, and there is no simple test for it. Older people tend to be more sensitive to the grapefruit effect, and too much active drug in the bloodstream can be dangerous for them.