Drugs and fruit juices - a combination to avoid

It has been common knowledge for a number of years that grapefruit juice can influence the absorption of certain drugs, potentially turning normal doses into toxic overdoses.

Now scientists say that grapefruit and other fruit juices such as orange and apple, can have the opposite effect by substantially decreasing the absorption of other drugs, potentially eliminating their intended beneficial effects.

This new evidence comes from the same researcher, Professor David G. Bailey, who made the discovery about the interaction between grapefruit and certain drugs.

This latest research has found that grapefruit juice and other juices decrease the oral absorption of certain drugs such as those prescribed for fighting life-threatening conditions such as heart disease, cancer, organ-transplant rejection, and serious infections.

The researchers say these drinks should be avoided by patients taking such drugs.

The new study represents the first controlled human studies of this type of drug-lowering interaction and Dr. Bailey the study leader, a professor of clinical pharmacology with the University of Western Ontario in London, Ontario, says the concern is the loss of benefit of medications essential for the treatment of serious medical conditions.

It was almost 20 years ago that Dr. Bailey and his colleagues found that grapefruit juice can dramatically boost the body's levels of the high-blood-pressure drug felodipine, causing potentially dangerous effects from excessive drug concentrations in the blood.

Other researchers have since identified almost 50 medications that carry the risk of grapefruit-induced drug-overdose interactions and now some prescription drugs carry warning labels against taking grapefruit juice or fresh grapefruit during the drugs' consumption.

For this recent research, Bailey's team had healthy volunteers take fexofenadine, an antihistamine used to fight allergies, along with either a single glass of grapefruit juice, water containing only naringin (substance in grapefruit juice that gives the juice its bitter taste), or water.

They found that when fexofenadine was taken with grapefruit juice, only half of the drug was absorbed compared to taking the drug with water alone.

Dr. Bailey says the loss of half of the amount of drugs taken into the body can be critical for the performance of certain drugs, and he believes this the mere beginning and that there are more drugs which are affected this way.

The research also showed that the active ingredient of grapefruit juice, naringin, appears to block a key drug uptake transporter called OATP1A2, which is involved in shuttling drugs from the small intestine to the bloodstream, this action reduces drug absorption and neutralizes their potential benefits.

However drugs whose levels are boosted in the presence of grapefruit juice appear to block an important drug metabolizing enzyme, called CYP3A4, that normally breaks down drugs.

So far it has been established that grapefruit, orange and apple juices have been shown to lower the absorption of etoposide, an anticancer agent; certain beta blockers (atenolol, celiprolol, talinolol) used to treat high blood pressure and prevent heart attacks; cyclosporine, a drug taken to prevent rejection of transplanted organs; and certain antibiotics (ciprofloxacin, levofloxacin, itraconazole).

Dr. Bailey says additional drugs are likely to be added to the list as physicians become more aware of this drug-lowering interaction.

The researchers say orange and apple juices also appear to contain naringin-like substances that inhibit OATP1A2, the chemical in oranges appears to be hesperidin, but the chemical in apples has yet to be identified.

Professor Bailey advises patients to consult with their doctor or pharmacist before taking any medications with grapefruit juice or other fruits and juices and says unless it is known to be a problem, take most medications only with water.

The research was funded by grants from the Canadian Institutes of Health Research and the United States Public Health Service and was presented this week at the 236th National Meeting of the American Chemical Society.

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