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How Grapefruit Juice aids in aborbsion.

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How Grapefruit juice works

Written by LewdTenant of AR.

When we take a medicine orally (by mouth), it has to get into our blood stream to do its job. (The medications that are intravenously administered, sidesteps this process and gets directly into the blood stream. That is why many of the medications that can be administered orally and intravenously, can be safely used in the intravenous route, while the oral route are subject to interactions.) The absorption usually takes place in the large or small intestines. The liver plays a key role in many of these metabolism b y removing a significant amount of the medication from the serum. For many medications, there is an optimum concentration of the active ingredient that need to be present in the serum for a certain amount of time for it to work. So, two factors are important. The maximum concentration of the active ingredient in the serum (called Cmax). The time factor is determined by plotting the concentration in the blood stream versus time and determining the area under the curve (AUC). Obviously, more AUC means we had been exposed to this ingredient for a longer time. Any mechanism that alters the optimum values of Cmax and AUC can affect the way the drug reacts. We will see later that grapefruit affects both Cmac and AUC for several prescription medications that take advantage of the Cytochrome P450 isoenzyme for the metabolism of the drug.

All drugs and many other substances within our body such as prostaglandins, fatty acids and steroids, utilize one or more of the cytochrome P450 isoenzymes in their respective metabolic (elimination) pathways. It turns out that one of the most important dietary factors that affects this isoenzyme is a bioflavinoid and possibly other ingredients contained in grapefruits and in grapefruit juice.


Grapefruit juice affects the bioavailability (therapeutic concentration) of a very wide variety of drugs. All drugs, to greatly differing degrees, achieve their respective target therapeutic levels by two main regulatory pathways, both involving one or more of the 30+ related cytochrome P450 isozymes.

The initial elimination route, called the presystemic "first-pass" metabolic pathway, involves the the gut (small intestine), the portal vein and the the liver. Depending on the drug or food supplement in question, this critical "first-pass" metabolic degradation will directly determine both the peak and mean concentrations of the drug or its metabolite in the blood stream.

Some drugs, such as terfenadine (Seldane) requires 100% breakdown by this presystemic "first-pass" metabolic pathway to convert it to its active and less toxic metabolite, terfenadine carboxylate. Any drug, (such as erythromycin, ketoconazole (Nizoral)) or food such as grapefruit juice, that inhibits or competes for the enteric (gut) cytochrome P-450 3A4 isozyme, will partially or completely block this metabolic step (breakdown) of terfenadine, and will result in the absorption of unmetabolized terfenadine, with the potential for very serious toxic reactions including ventricular tachyarrithmias (cardiac arrest) and death.

Approximately one hundred and twenty five deaths have now been linked to the concomitant use of terfenadine and one of the previously listed products that interferes with the Cytochrome P450 isoenzyme. Other drugs, e.g. prednisone, quinidine, theophylline, etc. with a high oral bioavailibility, or not competing for the same cytochrome P-450 3A4 isozyme, will not be affected by ingestion with grapefruit juice.

The second elimination pathway for all drugs involves the more predictable metabolic degradation over time by the hepatocytes in the liver, and excretion in the bile or by the kidneys. Grapefruit juice will not have any effect on the drugs that uses this second elimination pathway. It only affect the "first-pass" small intestine - liver metabolic pathway and not any secondary elimination metabolic processes. That is why some drugs are affected by grapefruit juice while others are not.


Dr. David Bailey and Associates at the University of Western Ontario, Canada showed that grapefruit juice acts by blocking (down regulating) the activity (expression) of cytochrome P450 3A4 isoenzyme in the intestinal wall, thereby preventing the presystemic "first-pass" oxidative metabolism (breakdown) for a wide variety of drugs. Grapefruit juice did not significantly block cytochrome P-450 3A4 isozymes in the liver hepatocytes. The net result of blocking this presystemic "first-pass" metabolic pathway, is the potential for a marked increase in the plasma concentration of the drug, often to the point of toxicity.

For example, in the case of a drug called felodipine (Renedil & Plendil) which they were investigating at the time, there was more than a five fold increase in the plasma concentration with grapefruit juice as compared with water.

Other studies with the cholesterol lowering drug, lovastatin (Mevacor), showed that grapefruit juice was capable of increasing the peak serum concentration of this drug up to 19.7-fold (range 5.2-19.7) and the area under the concentration-time curve (AUC) up to 26.3-fold (range 5.7-26.3).

The magnitude of the interaction with grapefruit juice appears to be highly variable among individuals, but the effect is relatively consistent for any given person. In addition, there appears to be considerable interracial genetic polymorphism of the cytochrome P450 isozyme subtypes.

The cytochrome P450 isoenzyme suppression activity of grapefruit juice was found to be accumulative, with an estimated half life at around 12 hours. The suppression effect at the enteric (gut) level, appears to be caused by a degrading (destruction) and not only suppression of the Cytochrome P450 3A4 isozyme. The return of cytochrome P450 3A4 isoenzyme activity appears to require de novo cytochrome P450 isozyme synthesis, further prolonging the effects of grapefruit juice.

Further studies have shown that grapefruit juice will also block other Cytochrome P450 isoenzymes, viz. 1A2 & 3A3. The magnitude of the effects from inhibition of cytochrome P450 1A2 & 3A3 isoenzyme activity by grapefruit juice is relatively minor in comparison to its 3A4 activity, and the clinical significance is relatively unknown.


The potential for this type of drug interaction is enormous. Dr. David Bailey, stated in the September 3rd, 1998 issue of the Medical Tribune:

"Sixty percent of drugs that are (commonly) prescribed are metabolized to some extent by this enzyme, CYP3A4 (Cytochrome P450 3A4). Many drugs undergo first-pass metabolism by CYP3A4. Hence, the inhibition of this enzyme in the gut causes plasma concentrations of these drugs to increase markedly after oral administration. The result can be significant. For example, taking one tablet of lovastatin (Mevacor) with a glass of grapefruit juice is the same as taking 12 to 15 tablets with a glass of water. Certain antihistamines, benzodiazepines, cyclosporin, caffeine, calcium antagonists and cisapride are among other drugs with which grapefruit interacts. So this interaction is very important and the list (of drugs) is going to continue to grow".

The list of specific drugs and drug types which interact with grapefruit juice is slowly expanding, but still very incomplete. We will take a look at few of these where clinical data is available.

Summary: Medications That are Affected by Grapefruit Juice Use

these are all substrates of Cytochrome P450

Statins (Cholesterol Lowering Drugs):

-Baycol (Cerivastatin)

-Mevacor (Lovastatin)

-Lipitor (Atorvastatin)

-Zocor (Simvastatin)



-Seldane (Terfenadine, taken off the U.S. market)

Calcium Channel Blockers (Blood Pressure Drugs):

-Nimotop (Nimodipine)


-Plendil (Felodipine)


-Sular (Nisoldipine)

Psychiatric Medications:

-Buspar (Buspirone)

-Halcion (Triazolam)

-Tegretol (Carbamazepine)

-Valium (Diazepam)

-Versed (Midazolam)

Intestinal Medications:

-Propulsid (Cisapride, taken off the U.S. market)

Immune Suppressants:

-Neoral (Cyclosporine)

-Prograf (Tacrolimus)

Pain Medications:


Impotence Drug:

-Viagra (Sildenafil)


-Losartan (for lowering blood pressure) - Grapefruit juice inhibits the body's ability to absorb the drug.

-Digoxin (for treating congestive heart failure) - Grapefruit juice inhibits the body's ability to absorb the drug.


Foods That Affect Cytochrome P450

The following foods are known to interact with cytochrome P450 isoenzyme. If you are taking any medication that utilizes P450 for its metabolism, you may want to avoide the following foods:



Fried and charcoal broiled foods




St John's Wort

HIV anti-virals







I believe the ones below are all inducers but did not have time to verify


Other Cruciferous Vegetables






Smoked fish or meat




Grapefruit's effect on medications is unpredictable. It may enhance the desired effect of the drug in some instances (so that we can take a lower amount of the drug and still get the effectiveness). It also means that if you take the suggested dose of the drug, our system gets a higher than expected concentration of the drug, resulting in amplification of the side effects of the drug and sometimes resulting in dangerous situations that was unforeseen at the time of the introduction of the drug in question. The same dose of drug could produce blood levels in different individuals ranging in concentration from normal to very toxic. Depending on the individual and the drug in question, dangerously high levels of the drug could enter the systemic circulation.

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Yes, just about any oral medication that is absorbed through the gut or intenstins will be effected. Also, the drugs metabolised through the liver will not be directly effected but will have less degredation in the gut; allowing more to be available in the liver.


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Originally posted by elitesnautica

Yes, just about any oral medication that is absorbed through the gut or intenstins will be effected. Also, the drugs metabolised through the liver will not be directly effected but will have less degredation in the gut; allowing more to be available in the liver.


yes but this is particually true with Xanax, to the point it can be life threatening. It can make the same amount more than twice as potent.

so lets say you are driving home and wired up so wash down a xanax with a bottle of grapfruit juice. You could easily sedate yourself to sleep or such imparement you cant drive.

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