Grapefruit components makes an interaction through the inhibition of CYP3A4-mediated metabolism (often first-pass metabolism), which increases concentrations of the drug. CYP3A4 is located in both the liver and the enterocytes (small intestine epithelial cells). One study concluded that a mechanism for the effect of grapefruit juice was a selective down regulation of CYP3A4 in the small intestine (See ref. N° 1).
Flavonoids and furanocoumarins present in grapefruit juice are thought to be the substances that can inhibit CYP3A4, although the exact components, which inhibit CYP3A4 enzymes, have not been clearly identified (See ref. N° 1).
Grapefruit components
One study has indicated that grapefruit juice contains six major constituents; naringin (NAR) the most prevalent flavonoid, naringenin (NGN) present as a conjugate in grapefruit juice, quercetin (QTN), 6´,7´-dihydroxybergamottin (DHB), bergamottin (BEG) and kaempferol.
Grapefuit: mechanism of interaction
The study investigated the effects of these constituents on saquinavir metabolism. It was determined that DHB and BEG inhibit CYP3A4-mediated metabolism in vitro and may also be responsible for the mechanism-based dose regulation of intestinal CYP3A4 caused by grapefruit consumption. DHB and NAR inhibited the P-glycoprotein (Pgp)-mediated drug efflux and this may contribute to the observed effects of grapefruit juice in vivo. However, a final decision on which flavonoid is the major active ingredient has not been reached (See ref. N° 1).
A second mechanism of interaction is possibly through Pgp. This is located in the apical brush border of the enterocytes. Pgp is a member of the adenosine triphosphate-binding cassette (ABC) super family of proteins. The role of the Pgp transporter is to carry lipophilic molecules from the enterocyte back into the intestinal lumen. After uptake by the enterocyte, many lipophilic drugs are either metabolised by CYP3A4 or pumped back into the lumen by the Pgp transporter. Pgp and CYP3A4 may act in tandem as a barrier to oral delivery of many drugs. Inhibition of either or both systems can increase the bioavailability of a drug. In vivo data show that grapefruit juice may activate Pgp in intestinal cell monolayers.
Therefore, if grapefruit juice has this activating effect on Pgp in vivo, reducing drug bioavailability might counteract the increased bioavailability seen with inhibition of CYP3A. However, clinical studies with grapefruit and cyclosporin have revealed conflicting evidence, suggesting that there may be in vivo inhibition of Pgp.
Grapefruit Grugs Interaction list
- Some statin drugs to lower cholesterol, such as Zocor (simvastatin) and Lipitor (atorvastatin).
- Some drugs that treat high blood pressure, such as Procardia and Adalat CC (both nifedipine).
- Some organ-transplant rejection drugs, such as Sandimmune and Neoral (both cyclosporine).
- Some anti-anxiety drugs, such as buspirone.
- Some corticosteroids that treat Crohn’s disease or ulcerative colitis, such as Entocort EC and Uceris (both budesonide).
- Some drugs that treat abnormal heart rhythms, such as Pacerone and Nexterone (both amiodarone).
- Some antihistamines, such as Allegra (fexofenadine). You can see further information about more drugs and its interaction with grapefruit on the table in the reference N° 1.
Considerations of Grapefruit consumption
- Ask your doctor, pharmacist or other health care provider if you can drink grapefruit juice while taking your medication.
- Read the medication guide or patient information sheet that comes with your prescription drug to find out if grapefruit juice affects your drug.
- Read the Drug Facts label on your OTC drug, which will say whether you shouldn’t have grapefruit or other fruit juices with it.
- If you must avoid grapefruit juice with your medicine, check the labels of fruit juices or drinks flavored with fruit juice to see whether they are made with grapefruit juice.
- Seville oranges (often used to make orange marmalade), pomelos, and tangelos (a cross between tangerines and grapefruit) may have the same effect as grapefruit juice. Do not eat those fruits if your medicine interacts with grapefruit juice. Some drugs, like statins used to lower cholesterol, are broken down by enzymes. As shown above, grapefruit juice can block the action of these enzymes, increasing the amount of drug in the body and may cause more side effects.
