Grapefruit Juice Used To Squeeze More Out Of Medications

November 19, 1997

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.

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."

# # # # # #

University of Michigan

Related Enzyme Articles from Brightsurf:

Repairing the photosynthetic enzyme Rubisco
Researchers at the Max Planck Institute of Biochemistry decipher the molecular mechanism of Rubisco Activase

Oldest enzyme in cellular respiration isolated
Researchers from Goethe University have found what is perhaps the oldest enzyme in cellular respiration.

UQ researchers solve a 50-year-old enzyme mystery
Advanced herbicides and treatments for infection may result from the unravelling of a 50-year-old mystery by University of Queensland researchers.

Overactive enzyme causes hereditary hypertension
After more than 40 years, several teams at the MDC and ECRC have now made a breakthrough discovery with the help of two animal models: they have proven that an altered gene encoding the enzyme PDE3A causes an inherited form of high blood pressure.

Triggered by light, a novel way to switch on an enzyme
In living cells, enzymes drive biochemical metabolic processes. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics.

A 'corset' for the enzyme structure
The structure of enzymes determines how they control vital processes such as digestion or immune response.

Could inhibiting the DPP4 enzyme help treat coronavirus?
Researchers and clinicians are scrambling to find ways to combat COVID-19, including new therapeutics and eventually a vaccine.

Bacterial enzyme could become a new target for antibiotics
Scientists discover the structure of an enzyme, found in the human gut, that breaks down a component of collagen.

Chemists create new artificial enzyme
Rajeev Prabhakar, a computational chemist at the University of Miami, and his collaborators at the University of Michigan have created a novel, synthetic, three-stranded molecule that functions just like a natural metalloenzyme, or an enzyme that contains metal ions.

First artificial enzyme created with two non-biological groups
Scientists at the University of Groningen turned a non-enzymatic protein into a new, artificial enzyme by adding two abiological catalytic components: an unnatural amino acid and a catalytic copper complex.

Read More: Enzyme News and Enzyme Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.