Re: [MOL] To Take or Not To Take Grapefruit Juice with your Meds... [00849]

NEW YORK, Apr 09 (Reuters Health) -- Many patients take their pills with a glass of grapefruit juice because they believe it raises levels of medication absorption into the bloodstream. However, a new report finds that in some cases, grapefruit juice may actually inhibit drug uptake.

"We now recognize (that) depending on the drug... grapefruit juice may either increase or decrease levels of drug in the blood," explain Dr. Leslie Benet and colleagues at the University of California at San Francisco. The findings are published in the April issue of the journal Pharmaceutical Research.

Previous research has suggested that compounds in grapefruit juice suppress the activity of CYP3A4, an intestinal enzyme that normally breaks down drug molecules before they enter the bloodstream. Those studies have shown that the consumption of grapefruit juice boosts levels of specific medications in the blood.

But the investigators noticed that "the magnitude of (this) increase is often insignificant, unpredictable and highly variable," depending on the drug. With some drugs, grapefruit juice had little or no 'boosting' effect, and, indeed, seemed to suppress medication absorption.

They noticed that absorption of all of these poorly affected drugs was closely related to the activity of another compound, P-glycoprotein.

Based on their experiments in the laboratory, Benet's team say they now have "evidence that grapefruit juice exposure enhances... P-glycoprotein activity" -- thereby inhibiting the absorption of numerous medications. These medications include HIV protease inhibitors, the anti-cancer agent vinblastine, cyclosporine (used in fighting organ rejection after transplant), the antihypertensive losartan, the heart medication digoxin, and the allergy drug fexofenadine.

In a statement from the American Association of Pharmaceutical Scientists, Benet said that "patients already taking grapefruit juice with their medications can continue to do so. However, for certain drugs we studied, such as immunosuppressives and HIV protease inhibitors, patients may get a further increase in absorption by taking their drugs a couple of hours after a glass of grapefruit juice."

"Patients who have not previously taken their drugs with grapefruit juice should be very cautious in doing so," the California researcher warned. As Benet explained, wide variations in drug absorption -- either too little or too much -- can be dangerous, "leading to potential concerns for toxicity or lack of efficacy."

SOURCE: Pharmaceutical Research 1999;478-485.