Page Banner

United States Department of Agriculture

Agricultural Research Service

Title: The Grapefruit Juice Effect: Grapefruit Juice and Drug Metabolism a Dynamic Relationship

Authors
item Stinson, W - FLORIDA DEPT OF CITRUS
item Widmer, Wilbur

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: May 16, 2003
Publication Date: N/A

Technical Abstract: In the late 1980s, scientists in Canada discovered that drinking grapefruit juice along with felodipine, a high blood pressure medicine, increased blood levels of the medication. Subsequent research showed that grapefruit juice contains constituents that inhibit the CYP3A4 enzyme in the small intestine that is involved with metabolizing certain prescription medications. When this enzyme is inhibited, drugs normally metabolized by CYP3A4 are more bioavailable, resulting in more of the affected drug being absorbed into the blood stream. The more extensively metabolized a drug is by the enzyme, the greater is the potential interaction with grapefruit juice. For a drug metabolized by intestinal CYP3A4, some individuals exhibit a large effect while others are only slightly affected. This is due to a natural variation in the amount of intestinal CYP3A4 among individuals. Drugs affected include calcium channel blockers (widely used to treat high blood pressure and cardiac disease), statins (widely used in lowering cholesterol), several immunosuppressants and psychiatric medications, and one antihistamine. The most compelling evidence to date indicates that furanocoumarins and furanocoumarin dimer compounds present in grapefruit juice are largely or entirely responsible for the interactions. Testing of a large number of retail grapefruit juice samples showed a wide variation in the amounts of these constituents. A study was then conducted where four grapefruit varieties were sampled throughout the 2001-2002 growing season in Florida and analyzed for furanocoumarin content. The Florida Department of Citrus has also supported clinical research to substantiate the constituents in grapefruit juice responsible for the effect, to better understand the recovery time of the CYP3A4 function after inhibition, and the effect of extended grapefruit juice consumption on human intestinal CYP3A4 activity. In addition, a major clinical study was funded to monitor the effect of grapefruit juice on patients already taking stable doses of the cholesterol lowering drug atorvastatin. The study was designed to determine if prescribed dosages could be lowered, if cholesterol would be further lowered for a prescribed dose, and safety issues with drinking grapefruit juice during treatments. By enhancing our knowledge about the "Grapefruit Juice Effect" the medical profession can better counsel their patients based on facts regarding the consumption of grapefruit juice with prescribed drugs. The opportunity exists to turn the "Grapefruit Juice Effect" into a major benefit for society.

Last Modified: 7/28/2014
Footer Content Back to Top of Page