PHILADELPHIA -- August 19, 2008 -- Evidence has been reported that grapefruit and other common fruit juices, including orange and apple, can substantially decrease the absorption of drugs, potentially wiping out their beneficial effects. It has been known for years that grapefruit juice can increase the absorption of certain drugs, turning normal doses into toxic overdoses.
The study provides evidence that patients should avoid drinking grapefruit juice and other juices when taking certain drugs, including some that are prescribed for heart disease, cancer, organ-transplant rejection, and infection, the researcher says. These findings -- representing the first controlled human studies of this type of drug-lowering interaction -- were described today at the 236th National Meeting of the American Chemical Society (ACS).
"Recently, we discovered that grapefruit and these other fruit juices substantially decrease the oral absorption of certain drugs undergoing intestinal uptake transport," says study leader David G. Bailey, PhD, University of Western Ontario, London, Ontario." The concern is loss of benefit of medications essential for the treatment of serious medical conditions."
Dr. Bailey's group had healthy volunteers take fexofenadine. The volunteers consumed the drug with either a single glass of grapefruit juice; water containing only naringin, the active ingredient of grapefruit juice; or water. When fexofenadine was taken with grapefruit juice, only half of the drug was absorbed compared with taking the drug with water alone, Bailey says. Loosing half of the amount of drugs taken into the body can be critical for the performance of certain agents, he points out.
They also showed that naringin appears to block a key drug uptake transporter, OATP1A2, which is involved in shuttling drugs from the small intestine to the bloodstream. Blocking this transporter reduces drug absorption and neutralises its potential benefits, the researchers say. By contrast, drugs whose levels are boosted in the presence of grapefruit juice appear to block the enzyme CYP3A4, which normally metabolises drugs.
"This is just the tip of the iceberg," Dr. Bailey says. "I'm sure we'll find more and more drugs that are affected this way."
To date, grapefruit, orange, and apple juices have been shown to lower the absorption of the anticancer agent etoposide; certain beta blockers (atenolol, celiprolol, talinolol); cyclosporine, given to prevent rejection of transplanted organs; and certain antibiotics (ciprofloxacin, levofloxacin, itraconazole). Additional drugs are likely to be added to the list as physicians become more aware of this drug-lowering interaction, Dr. Bailey says.
Orange and apple juices also appear to contain naringin-like substances that inhibit OATP1A2, Bailey says. The chemical in oranges appears to be hesperidin, but the chemical in apples has not yet been identified, the researchers note.
Dr. Bailey advises patients to consult their doctor or pharmacist before taking any medications with grapefruit juice or other fruits and juices. He recommends taking most medications only with water.
This research was funded by grants from the Canadian Institutes of Health Research and the US Public Health Service.
SOURCE: American Chemical Society
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