Grapefruit Opens Door to Excess Medication Dosage

Milwaukee Journal Sentinel

(KRT)

MILWAUKEE - If Lipitor, Viagra or Pletal claims a spot in your medicine cabinet, chances are you've been warned not to drink grapefruit juice.

Doctors, pharmacists and drug labels deliver that message with more than 20 common medications. And most hospitals have removed the juice from their menus.

So how did the otherwise super-fruit, touted for its ability to fight cancer and heart disease, become known for causing toxicity, irregular heartbeats, low blood pressure and possibly even death?

It's all about chemistry.

Not all of the medicine you swallow gets into your bloodstream to take action. A portion gets broken down along the way and goes to waste. Drug-makers consider that when calculating drug dosages.

Grapefruit reacts with drugs that are largely broken down in the small intestine before they have a chance to get to the bloodstream. Many of these drugs bind to a type of enzyme, referred to as CYP3A4, and get metabolized.

Imagine the enzyme is a vault guard. Chemicals from the grapefruit juice act as a diversion that draws the guard away from the vault - the bloodstream. While the guard is occupied, a thief - the drug - is able to sneak through the door.

The end result: People who take these drugs with grapefruit juice get a higher dosage than their doctors prescribed.

This interaction was discovered in 1989 by University of Western Ontario researchers who used grapefruit juice to cover the taste of alcohol in a study of felodipine, a blood pressure medication. They found the dosage was multiplied as much as three times because of the grapefruit juice effect. Since then, numerous studies have been done to determine which drugs are affected, by what mechanism and to what extent.

Scientists used to think a chemical called naringin, the same one that makes grapefruit so bitter, was responsible for the grapefruit juice effect. But researchers did not observe the heightened dosage when they tested naringin alone, said Dean Elbe, a clinical pharmacist at the Richmond Hospital Pharmacy Department in Vancouver, British Columbia, and an expert in the area of grapefruit juice/drug interactions.

They've narrowed the effect down to a chemical in a family called furanocoumarins, he said, which also have been linked with toxicity problems in celery plants.

Even a single, 8-ounce glass of either white, pink or red grapefruit juice has been shown to be enough to cause a significant effect, Elbe said. And the body won't return to normal for up to 72 hours after drinking the juice, he said.

Researchers also have determined that grapefruit themselves can cause the effect.

"Those who are avoiding grapefruit juice should avoid grapefruit as well," said Sarah Bland, a clinical pharmacist at the University of Wisconsin Hospital and Clinics' Center for Drug Policy in Madison.

Seville oranges also can cause the grapefruit juice effect, researchers say. The bitter oranges are sometimes found in marmalade but not in American orange juice. But the amount in marmalade is not significant enough to cause the effect, Elbe said.

Given the high cost of prescriptions and the possibility for grapefruit-induced higher dosages, it might seem like a great idea to take these drugs with grapefruit juice. But the level of the drug-metabolizing enzyme can differ greatly from person to person, Elbe said, so you cannot predict how much of the drug will reach the bloodstream.

If you are eating grapefruit while taking one of the affected medications, don't panic.

"You don't want to have a sudden change in habits," Bland said. If people are taking medications while regularly eating grapefruit or drinking grapefruit juice, they should continue their regimen, she said. But for patients getting these medications for the first time, she said, "then it's probably best to have them avoid grapefruit altogether."

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(c) 2003, Milwaukee Journal Sentinel. Distributed by Knight Ridder/Tribune News Service.