Grapefruit juice furanocoumarins and p450 cytochrome CYP3A4

Paul F. Cancalon, Carl Haun

Abstract


It has been reported in several studies that the blood levels of some drugs can be significantly higher in patients who have consumed grapefruits or grapefruit juice. These drugs have in common the fact that they are metabolized in the intestine by an enzyme of the P450 cytochrome family, CYP3A4. This enzyme is located in the liver and in the nutrient absorbing cells lining the intestine (enterocytes). The increase in drug bioavailability is due to the removal from the intestine of the CYP3A4 enzyme by grapefruit compounds called furanocoumarins (FC) and some of their homo and hetero dimers. The mechanism responsible for these increases in drug blood levels by grapefruit juice has been largely elucidated. Under normal conditions, intestine CYP3A4 catabolizes many xenobiotics including some drugs. In extreme cases, most of an ingested drug is destroyed and only a very small amount may reach its target. Following grapefruit absorption, the FCs are modified by CYP3A4 and the resulting FC metabolites bind the enzyme, tagging it for destruction. New CYP3A4 enzymes will reappear about three days later, in new enterocytes, when the old cells are replaced. When CYP3A4 is absent from the intestine, the transfer of some drugs into the blood stream is no longer inhibited and has been shown to rise significantly. Even among those drugs, the effect of grapefruit on blood level increases has been shown to range from zero to up to ten folds in a few cases. To clarify this problem a web site has been created, which classifies drugs according to their level of interaction with grapefrui (http://www.druginteractioncenter.org). It is therefore important for a patient to consult a physician and also such a site to determine if the drugs taken are affected or not by grapefruit. In most cases, a specific condition can be treated with a drug not affected by grapefruit.

Keywords


drug interaction; drug bioavailability; intestine

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Proc. Fla. State Hort. Soc.     ISSN 0886-7283