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ShareFeb. 9, 2001 — Chapel Hill -- Since the early 1990s, doctors have known that certain drugs -- including commonly taken medications for lowering cholesterol and blood pressure -- become much more effective when people who take them also drink a glass of grapefruit juice at the same time. That power of grapefruit juice can be beneficial, but also can be harmful in some situations.
Now, a new study shows Seville oranges can do the same thing. Although not generally drunk as juice because of their sour taste, the ancient fruits -- imported to Spain from Asia during the Crusades - are used widely in condiments and marmalade.
"This is the first demonstration that a fruit other than grapefruit can have the same effect on drugs," said Dr. Paul B. Watkins, professor of medicine at the University of North Carolina at Chapel Hill School of Medicine. "Our work raises anew the probability that other fruits will be found that do the same thing."
Watkins said he believes the study also identifies the major active ingredient in grapefruit responsible for making the drugs stronger.
"Because of the variability involved in grapefruit juices, everyone has been trying to figure out what causes the effect so that we can add that compound directly to pills instead," Watkins said. "Our prior research suggested that a compound called DHB (dihydroxybergamottin) was an active ingredient."
He and colleagues could not test a purified form of DHB in study volunteers because the Food and Drug Administration has not approved it as a drug yet, he said. They instead chose Seville orange juice since it contains comparable amounts of DHB. "Our study is strong evidence that DHB is the major active ingredient in grapefruit responsible for making certain drugs more effective." From past studies, researchers already know that other, naturally sweeter orange juices consumed in the United States do not contain DHB and do not boost drug effects. Dr. David Edwards, a scientist at Wayne State University, discovered the DHB molecule and has applied for a patent on it. A report on the new findings appears in the current issue of the journal Clinical Pharmacology and Therapeutics. Besides Watkins, authors are UNC doctoral student Shefali Malhotra, Dr. David G. Bailey of the University of Western Ontario, who discovered grapefruit's drug-boosting action, and Dr. Mary F. Paine, research assistant professor of pharmacy at UNC.
While working in Michigan several years ago, Watkins found that the growing list of drugs affected by grapefruit juice have one thing in common. That is that they are chewed up by the same intestinal enzyme, CYP3A4, which Watkins also discovered.
"It turns out that if you drink a glass of grapefruit juice, this enzyme disappears, and so more of a drug is absorbed and acts in the body," he said.
In the new study, the research team had 10 healthy volunteers drink grapefruit juice, common orange juice or a sweetened form of Seville orange juice after receiving a single oral dose of felodipine, a drug to lower blood pressure. Then they repeated the procedure twice so that all subjects received each of the juices, along with the medication, at least a week apart.
The scientists then measured the amount of drug in subjects' blood 12 times over 24 hours. Analysis showed peak concentrations of felodipine to be close to twice as high when the volunteers drank juice from grapefruits or Seville oranges as when they drank only common orange juice.
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The above story is reprinted from materials provided by University Of North Carolina At Chapel Hill.
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