Grapefruit juice affects absorption of drugs

An apple a day may keep the doctor away, but recently, certain substances in grapefruits have been the target of extensive research by University doctors.

The substances, called furanocoumarins, attach themselves to enzymes in the small intestine and increase the absorption of some drugs into the human body - an effect that can be both positive and negative.

The furanocoumarins "essentially destroy a particular metabolic pathway in the intestine," said Medical Prof. Paul Watkins, director of the General Clinical Research Center.

"Just a few drugs are affected by grapefruit juice," Watkins said. These drugs are also interact with erythromycin, a common antibiotic. Erythromycin "does the same thing as grapefruit juice, but is much more potent," Watkins said.

Watkins added various components of grapefruit juice to cell cultures to determine which compounds were attaching themselves to intestinal enzymes.

The major active ingredient of grapefruit juice is 6',7'-dihydroxybergamottin (DHB). The second compound, FC726 also destroys the enzyme like DHB, but seems to be more selective in what it does, Watkins said.

"Right now we're investigating 15 different chemicals to determine how specific their effects are," Watkins said.

There are "many implications for the discovery in pharmacy and medicinal chemistry - medications could be potentially enhanced," said chemistry Prof. Rich Lawton.

After the compound selective for this small intestine enzyme is identified, it must be purified, approved for clinical trials and reviewed for approval by the Food and Drug Administration before it is added to drugs, said University researcher Michael Fitzsimmons.

One of the current AIDS-fighting drugs on the market is often taken with grapefruit juice to increase drug absorption. "It's actually suggested that patients take the drug with grapefruit juice," Watkins said.

Because of differences between brands, however, drinking raw juice is an unreliable method for administering the chemical into the body.

"If you're used to taking medications with grapefruit juice, there is no reason to stop," Watkins said.

But it could be dangerous to start drinking grapefruit juice with medications without asking a physician about possible interactions. One Michigan resident drank grapefruit juice with his antihistamine, which "built up in his blood and the gentleman died," Fitzsimmons said.

Future research may determine which furanocoumarins could be added to drugs to enhance their effects and reduce the amount of drug. "It's hard to say where science is going," Fitzsimmons said.

"I think there will be a commercial market for this compound," Watkins said. "It seems to give a more reliable oral delivery of drugs."

12-10-97