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David Baxter

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Drug interaction substances in grapefruit juice identified
Wed, May 10 2006

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 anxiety, depression, 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."

See Grapefruit Juice Affects Some Rx Drugs for a list of commonly prescribed drugs known to be affected by grapefruit juice. The Grapefruit - Drug Interactions website's Dean Elbe BSc (Pharm), BCPP has a more comprehensive list (Adobe Acrobat PDF file, 111KB).

Sourec: Paine MF, Widmer WW, Hart HL, Pusek SN, Beavers KL, Criss AB, Brown SS, Thomas BF, Watkins PB. A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction
Am J Clin Nutr. 2006 May, 83(5):1097-1105. [[url=http://www.ajcn.org/cgi/content/abstract/83/5/1097]Abstract
]
 

Retired

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It's been a long time coming, and it's good to know the mechanism of action of this important interaction has been identified.

Another medication subject to grapefruit warnings is Fosamax, taken by peri and post menopausal women to increase bone density.

Amazingly, this remarkable food-drug interaction was discovered completely by accident over a decade ago! Researchers were investigating whether alcohol could interact with felodipine (Plendil) and used a solution of alcohol with grapefruit juice to mask the taste of alcohol for the study. Researchers discovered that blood levels of felodipine were increased several fold more than in previous studies. This increased blood level caused an increase in the effect and side effects of felodipine. Further research revealed that the grapefruit juice itself was actually increasing the amount of the study drug in the body.

Some drugs subject to this interaction are listed on Medicine Net

But the news about grapefruit juice is not all bad. For example, the absorption of cyclosporine, a drug given to organ-transplant patients, can actually be enhanced. Without help, not much cyclosporine is absorbed into the body because P-gp and CYP3A kick it out or destroy it before it gets a chance to do its job. Low blood levels of cyclosporine can lead to organ rejection. Source
 

David Baxter

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That's very intersting about the cyclosporine, TSOW. I didn't know that.
 

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