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Study identifies substances in grapefruit juice that interact dangerously with some drugs


New research from the University of North Carolina at Chapel Hill has identified and established the substance in grapefruit juice that causes potentially dangerous interactions with certain medications.

For almost a decade, people have been told by their doctors and pharmacists to avoid grapefruit juice if they are being treated with certain medications, including some drugs that control blood pressure or lower cholesterol. Studies have shown that grapefruit juice can cause more of these drugs to enter the blood stream, resulting in undesirable and even dangerous side effects.

The drugs affected by grapefruit juice usually have some difficulty entering the body after they are consumed because an intestinal enzyme, CYP3A, partially destroys them as they are absorbed. Grapefruit juice, but not other commonly consumed fruit juices, inhibits this enzyme, allowing more of these drugs to enter the body.

It was originally assumed that the ingredients responsible for drug interactions were the flavonoids that give grapefruit juice its bitter taste.

The new study shows that a group of chemicals called furanocoumarins are the likely culprit.

"This is the best evidence to date that furanocoumarins are the active ingredients in grapefruit juice that cause the interaction with medications," said Dr. Paul Watkins, the Dr. Verne S. Caviness distinguished professor of medicine and director of UNC’s General Clinical Research Center (GCRC). Watkins led the study team.

A report of the new findings appears in the May issue of the American Journal of Clinical Nutrition.

To determine whether furanocoumarins are responsible for grapefruit juice-drug interactions, Watkins worked with scientists at the Florida Department of Citrus to selectively remove only the furanocoumarins from the juice. He and his collaborators then studied the effect of the whole juice versus furanocoumarin-free juice on the ability to affect absorption of felodipine, an anti-hypertension drug known to interact with grapefruit juice "And we found that removing the furanocoumarins from grapefruit juice entirely got rid of this interaction," Watkins said.

In this randomized study, 18 healthy volunteers took 10 milligrams of felodipine with each of three juices: orange juice, regular grapefruit juice, and grapefruit juice devoid of furanocoumarins. Blood was collected over 24 hours to measure felodipine blood levels. One week elapsed between each felodipine-juice "treatment."

The study found that in contrast to whole grapefruit juice, the furanocoumarin-free grapefruit juice behaved like orange juice and did not cause an interaction with felodipine.

Watkins notes that there are several implications of this work.

"First, it should now be possible to market the furanocoumarin-free grapefruit juice to patients who would otherwise need to avoid grapefruit. In addition, it should be possible to screen new foods for the potential for drug interactions by determining whether they contain furanocoumarins.

"Finally, it may be possible to add furanocoumarins to formulations of certain drugs that tend to be poorly or erratically absorbed to improve their oral delivery."

Leslie H. Lang | EurekAlert!
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