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Scientists Discover Substances That Make Grapefruit Juice Squeeze More Out Of Some Medications

Date:
November 20, 1997
Source:
University Of Michigan
Summary:
Researchers, led by a team from the University of Michigan Medical Center, have isolated a pair of substances in grapefruit juice that cause greater absorption of certain drugs in the human body.

ANN ARBOR---Researchers, led by a team from the University of Michigan Medical Center, have isolated a pair of substances in grapefruit juice that cause greater absorption of certain drugs in the human body. The new findings are published in the November issue of the journal Drug Metabolism and Disposition.

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Earlier studies found that patients who took certain medications with grapefruit juice absorbed more of the medicine. The key to how grapefruit juice enhances drug absorption lies in the interaction between the grapefruit juice and an enzyme found in the small intestine.

Now, Paul B. Watkins, M.D., director of the U-M General Clinical Research Center, and his colleagues have isolated two substances in grapefruit, called furanocoumarins (few-ran-oh-COO-muh-rinns), that are responsible for the so-called grapefruit effect. Watkins says the two components act like suicide bombers, attaching themselves to the enzyme and destroying its ability to interfere with drug absorption.

The enzyme, known as CYP3A4, normally acts as a sort of gatekeeper against certain types of medication, including those prescribed for high blood pressure, heart disease, allergies, AIDS and organ transplantation. These types of drugs, unlike most medications, are not absorbed efficiently in the intestines because they are largely broken down by CYP3A4 in the intestinal wall. Watkins says people typically have varying levels of the enzyme in their intestines---which appears to explain why some individuals absorb greater amounts of a given medication than others.

Watkins says the two furanocoumarins have different properties. The major active substance in grapefruit juice is called 6',7'-dihydroxybergamottin (DHB) and the researchers named the other ingredient they discovered FC726. Where the two differ is that DHB appears to have multiple effects, while FC726 seems to work specifically on the CYP3A4 enzyme.

Watkins says these findings could have important ramifications for the future of drug-making. Researchers now believe that by adding one of the furanocoumarinscontained in grapefruit to certain oral medications, the reliability and safety of the drugs can be noticeably improved. "This discovery allows for the development of improved oral medications, not just for existing drugs, but more importantly, drugs that would not have made useful oral medications without this prior understanding," Watkins says. "By placing DHB or FC726 directly into a pill, much more of the drug will be absorbed in a reliable manner."

Another interesting finding in the study was that the concentration of the active ingredients varies dramatically among grapefruits and grapefruit juices, even within the same product line. This is most likely because of growing conditions in different regions and because manufacturers typically buy their grapefruits from many areas. "For this reason," Watkins says, "it would be preferable to add the active ingredient to pills, rather than just taking medication with grapefruit products."

Watkins believes there are probably additional substances in grapefruit that control drug absorption. "The direction of the research now," he says, "is to continue to search for these furanocoumarins to find the magic bullet, the one that just does what we want it to without interfering with anything else. We believe the grapefruit harbors all kinds of compounds that will be useful in formulating different kinds of drugs."


Story Source:

The above story is based on materials provided by University Of Michigan. Note: Materials may be edited for content and length.


Cite This Page:

University Of Michigan. "Scientists Discover Substances That Make Grapefruit Juice Squeeze More Out Of Some Medications." ScienceDaily. ScienceDaily, 20 November 1997. <www.sciencedaily.com/releases/1997/11/971120071626.htm>.
University Of Michigan. (1997, November 20). Scientists Discover Substances That Make Grapefruit Juice Squeeze More Out Of Some Medications. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/1997/11/971120071626.htm
University Of Michigan. "Scientists Discover Substances That Make Grapefruit Juice Squeeze More Out Of Some Medications." ScienceDaily. www.sciencedaily.com/releases/1997/11/971120071626.htm (accessed October 30, 2014).

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