Grapefruit juice, well established to interfere with some drugs such as the high-blood-pressure drug felodipin, but new research suggests that it may also affect the absorption of anti-allergy drugs.
Researchers from the University of Western Ontario in London, Ontario told attendees at the 236th National Meeting of the American Chemical Society that the compound naringin appeared to be at the centre of the issue.
Moreover, orange and apple juices also appear to contain naringin-like substances that may inhibit drug activity, said lead researcher David Bailey, PhD.
"This is just the tip of the iceberg," said Bailey. "I'm sure we'll find more and more drugs that are affected this way."
If further research backs up these preliminary results, it could lead to more warning labels on pharmaceutical products to avoid certain fruit juices.
The “Grapefruit Juice Effect” was first observed about 20 years ago when researchers noted that the fruit juice increased the absorption of felodipine, thereby causing potentially dangerous effects from excessive drug concentrations in the blood.
The new study reports for the first time that the juice may also lower the activity of a certain drug, according to a controlled human study.
Bailey and co-workers administered the antihistamine fexofenadine to healthy volunteers. They consumed the drug with either a single glass of grapefruit juice, water containing only naringin, or water. They told attendees at the ACS national meeting that grapefruit juice reduced absorption by 50 per cent, compared to water.
Loosing half of the amount of drugs taken into the body can be critical for the performance certain drugs, added Bailey.
"Recently, we discovered that grapefruit and these other fruit juices substantially decrease the oral absorption of certain drugs undergoing intestinal uptake transport," he said
"The concern is loss of benefit of medications essential for the treatment of serious medical conditions."
Interfering with drug transport
Grapefruit juice appears to act via one of two avenues, said the researchers. Inhibition of absorption was linked to naringin blocking the drug uptake transporter OATP1A2, which shuttles drugs from the small intestine to the bloodstream.
On the other hand, the juice may also block the enzyme CYP3A4 that plays an important role in metabolising drugs. This leads to an increase in blood levels of the drug.
Beyond grapefruit
The body of science linking certain fruit juices to drug interactions is growing with studies already linking grapefruit, orange and apple juices to lower absorption of the anti-cancer agent etoposide, certain beta blockers (atenolol, celiprolol, talinolol), the anti-transplant rejection drug cyclosporine, and certain antibiotics (ciprofloxacin, levofloxacin, itraconazole).
The researchers warned that this list may grow as more studies are performed.
While naringin is identified as the problem in grapefruit, the researchers note that the chemical in oranges could be hesperidin, while they do not know what the chemical in apples is.
The research was funded by grants from the Canadian Institutes of Health Research and the United States Public Health Service.
Commenting independently on the research, Professor James Ritter from King's College London, told the BBC: "The observation is very interesting. It will need more work to establish how important such interactions are in clinical practice and for what drugs and juices."