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Medicine Squeezes Secrets from the Grapefruit

Medical researchers have known for some time that eating a grapefruit-or drinking a glass of grapefruit juice-can dramatically increase the effects of certain common drugs. But no one knew why. Now researchers at the University of Michigan in Ann Arbor, led by internist Paul B. Watkins, have identified compounds in grapefruits called furanocoumarins that explain grapefruit’s mysterious power.

Furanocoumarins work by blocking an enzyme (CYP3A4) that chews up certain chemicals in the intestine-as well as some drugs. Physicians don’t recommend washing down pills with grapefruit juice because the effect varies from person to person. But the discovery of the compounds responsible for grapefruit’s powers could provide critical clues to increasing the absorption of drugs. And that could mean patients would need far lower doses of some extremely expensive drugs.

That’s the goal of researchers at AvMax, a two-year-old biotech company in Berkeley, Calif. The company, which holds a patent on the furanocoumarins and boasts Watkins as a scientific advisor, is using furanocoumarins as a model to design ways to block the enzyme temporarily.

So far, AvMax scientists have made inhibitors of CYP3A4 and have shown in animal studies that the compounds boost absorption. They’re planning a future clinical trial to test the possibility of using the enzyme blockers with protease inhibitors (medication used to treat AIDS patients). Protease inhibitors carry the hefty price tag of $12,000 a year, yet just 5 percent of the drug is absorbed.

Another goal at AvMax is to use the insight gained from furanocoumarins to convert intravenous medications. Most drugs that are given in intravenous form are not absorbed at all when given orally (indeed that’s the reason they’re given the painful way). If this work pans out, many fewer patients will be experiencing the pain of the needle-just one of the potential medical benefits of the humble grapefruit.

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