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Substance from Grapefruit Juice May Make Medications Safer

A single glass of grapefruit juice can significantly increase the absorption of a number of commonly used oral medications, researchers have found. These drugs include nearly all calcium channel blockers (used to control blood pressure) and some immunosuppressants, sedatives, and protease inhibitors (used to treat AIDS).

Although the "grapefruit juice effect" was discovered serendipitously almost a decade ago when scientists gave volunteers grapefruit juice to mask the taste of a medication, researchers did not know how the effect worked. Now, Dr. Paul Watkins, Dr. Kenneth Lown, and their colleagues at the University of Michigan Medical Center in Ann Arbor report in the May 15 issue of the Journal of Clinical Investigation that grapefruit juice works by decreasing the amount of an enzyme called CYP3A4 that is present in the small intestine. This finding is important because it narrows the search for the substance in grapefruit juice that is responsible for its effects on drug metabolism. Isolating this substance could enable manufacturers to produce safer and more effective medications.

One of the most interesting findings from the University of Michigan study is that, after taking grapefruit juice, CYP3A4 levels were virtually the same for everyone in the study. This is important because, normally, there are large differences in CYP3A4 levels between individuals, which, in turn, affect their metabolism of drugs. Thus, a dose of a drug that may be effective for one individual can be toxic to another. Addition of the active substance in grapefruit juice to a medication could produce a drug for which a standard dosage would be equally effective in everyone.

What should people who regularly take drugs that are metabolized by CYP3A4 do? "Consistency is the key," Dr. Lown says. "If you regularly drink grapefruit juice, don't change. If you are on these drugs and don't normally take them with grapefruit juice, you may need to consu
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Contact: Doris Brody
brodyd@gm1.nigms.nih.gov
301-496-7301
NIH/National Institute of General Medical Sciences
15-May-1997


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