CHAPEL HILL, N.C., May 10 -- Those dangerous interactions when grapefruit juice is mixed with some drugs are apparently triggered by members of a family of plant toxins called furanocoumarins, according to researchers here.
Grapefruit juice contains several furanocoumarins, Paul Watkins, M.D., of the University of North Carolina and colleagues reported in the May issue of the American Journal of Clinical Nutrition. Remove them, and the juice-drug interactions are neutralized, they added. And the juice is sweeter.
The furanocoumarins include bergamottin and 6',7'-dihydroxybergamottin (DHB), which have been shown to inhibit drug metabolism by interfering with hepatic cytochrome P450 3A4 (CYP3A4), increasing systemic exposure to drugs such as cyclosporine, some statins, and some calcium channel blockers.
Dr. Watkins and colleagues reported that grapefruit juice modified to have little or no furanocoumarin content was roughly equivalent to orange juice in its ability to interfere with the CYP3A4-mediated metabolism of Plendil (felodipine), the calcium channel antagonist that was the first medication recognized to interact with grapefruit juice.
"Removing the furanocoumarins from grapefruit juice entirely got rid of this interaction," Dr. Watkins said. Interestingly, the modified grapefruit juice, the investigators reported, appeared to be sweeter and less bitter than normal juice.
The research has several implications, Dr. Watkins said. "First, it should now be possible to market the furanocoumarin-free grapefruit juice to patients who would otherwise need to avoid grapefruit. In addition, it should be possible to screen new foods for the potential for drug interactions by determining whether they contain furanocoumarins."
Also, he said, "it may be possible to add furanocoumarins to formulations of certain drugs that tend to be poorly or erratically absorbed to improve their oral delivery."
The researchers first used filtration techniques to remove the furanocoumarins selectively from grapefruit juice; other major components were retained, including the flavonoids that give the juice its distinctive bitter taste. Flavonoids were initially thought to be the culprits in the drug interactions, but that theory was disproved in 1992, the researchers noted.
The furanocoumarin-free juice was then tested against orange juice and normal grapefruit juice in a small randomized crossover study, involving 18 healthy volunteers, Dr. Watkins and colleagues reported.
The volunteers were given 10 mg of Plendil together with 240 mL of one of the juices. Blood was collected over 24 hours to measure Plendil blood levels and a week was allowed to elapse before each volunteer tried the drug with another type of juice.
The volunteers were randomly assigned to one of the six possible orders in which the juice-Plendil combinations could be drunk, the researchers noted.
Because orange juice was previously shown to have no interaction with Plendil, it was used as a control.
The study showed that the area under the plasma concentration/time curve (AUC) for Plendil -- a measure of how quickly the drug was metabolized -- was not significantly different for orange juice or furanocoumarin-free grapefruit juice. On the other hand, the AUC for normal grapefruit juice was significantly higher (30% to 370%) than that for furanocoumarin-free juice or orange juice (P 'less than' 0.001).
The maximum concentration of Plendil was also significantly greater (P 'less than' 0.001) with consumption of grapefruit juice (21 [7.6-50] nmol/L) compared with orange juice (7.6 [3.4-13.9] nmol/L) and furanocoumarin-free grapefruit juice (8.3 [3.0-16.6] nmol/L)
-------------------- Jenifer Stolow LymeNet.Org Webmaster Posts: 318 | From Upstate New York, USA | Registered: Feb 2001
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Ann-OH
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Thanks, for making this "postable" Jenifer. Not sure it belongs in General Support as I was trying to post it in response to something on Medical. I hope people will get the point anywhere.
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