I came across this info. when I was researching the effects of grapefruit juice on the absorption of some medications. I have started drinking it with my orals. What do you all think?
How Grapefruit juice works
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.
INTERACTIONS OF GRAPEFRUIT WITH MEDICATIONS
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.
INTERACTIONS OF GRAPEFRUIT WITH MEDICATIONS
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.
INTERACTIONS OF GRAPEFRUIT WITH MEDICATIONS
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)
Antihistamines:
-Ebastine
-Seldane (Terfenadine, taken off the U.S. market)
Calcium Channel Blockers (Blood Pressure Drugs):
-Nimotop (Nimodipine)
-Nitrendipine
-Plendil (Felodipine)
-Pranidipine
-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:
-Methadone
Impotence Drug:
-Viagra (Sildenafil)
Miscellaneous
-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.
INTERACTIONS OF GRAPEFRUIT WITH MEDICATIONS
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:
Inducers
Broccoli
Fried and charcoal broiled foods
Insulin
tobacco
ethanol
St John's Wort
HIV anti-virals
barbituates
prednisone(corticosteroid)
Inhibitors
ketoconazole(Nizoral)
cocaine
Grapefruit
I believe the ones below are all inducers but did not have time to verify
Cabbage
Other Cruciferous Vegetables
Spinach
Leeks
Onion
Garlic
Parsley
Smoked fish or meat
Ham
Sausage
Conclusion
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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Grapefruit Juice To Enhance Absorption:
Started By BD100, Sep 15 2004 03:45 PM
13 replies to this topic
#2 Guest_in review_*
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Posted 15 September 2004 - 04:52 PM
A little more info for you on it brother man it is good stuff!!!! Has been known to give some meds a 500% increase in absorbtion!!!!!!!!!!
Grapefruit juice interacts with a number of medications. This unusual discovery was made serendipitously in 1989 during an experiment designed to test the effect of ethanol on a calcium-channel blocker.1 The observed response was later determined to be due to the grapefruit juice delivery vehicle rather than the alcohol. In the past decade, the list of drug interactions with grapefruit juice has expanded to include several classes of medication, precipitating a recent advisory from Health Canada.2
The interaction: As little as 250 mL of grapefruit juice can change the metabolism of some drugs.3 This drug–food interaction occurs because of a common pathway involving a specific isoform of cytochrome P450 — CYP3A4 — present in both the liver and the intestinal wall. Studies suggest that grapefruit juice exerts its effect primarily at the level of the intestine.4
After ingestion, a substrate contained in the grapefruit binds to the intestinal isoenzyme, impairing first-pass metabolism directly and causing a sustained decrease in CYP3A4 protein expression.5 Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours.6 The net result is inhibition of drug metabolism in the intestine and increased oral bioavailability. Because of the prolonged response, separating the intake of the drug and the juice does not prevent interference.
Individuals express CYP3A4 in different proportions, those with the highest intestinal concentration being most susceptible to grapefruit juice–drug interactions.5 An effect is seen with the whole fruit as well as its juice, so caution should be exercised with both.7 The precise chemical compound in grapefruit that causes the interaction has not been identified. There is no similar reaction with orange juice, although there is some suspicion that "sour oranges" such as the Seville variety, may have some effect.8 A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.9
There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability.3 The limitation is the individual variation in patient response. However, if the chemical that causes grapefruit's CYP3A4 inhibition is elucidated, there may be an opportunity to modulate that pathway in a controlled fashion.
What to do: Much of the data obtained on grapefruit juice–drug interactions involved measuring serum drug concentrations in small numbers of healthy volunteers. Because of the limited data and only occasional case reports,10 it is difficult to quantify the clinical significance for individual patients. One may assume that the interaction occurs primarily with oral medicines, and only with those that share the CYP3A4 metabolism pathway, with the consequence being increased oral bioavailability, higher serum drug concentrations and associated adverse effects.
Physicians should review medication lists often, with the goal of warning patients about adverse interactions. A list of medicines with which patients should not consume grapefruit is provided in Table 1.3,11,12 In the case of several medications that share the CYP3A4 metabolism pathway, but for which a clinical effect has not been elucidated or is theoretical, patients should be advised to consume grapefruit cautiously and be monitored for toxicity.
O N E
Grapefruit juice interacts with a number of medications. This unusual discovery was made serendipitously in 1989 during an experiment designed to test the effect of ethanol on a calcium-channel blocker.1 The observed response was later determined to be due to the grapefruit juice delivery vehicle rather than the alcohol. In the past decade, the list of drug interactions with grapefruit juice has expanded to include several classes of medication, precipitating a recent advisory from Health Canada.2
The interaction: As little as 250 mL of grapefruit juice can change the metabolism of some drugs.3 This drug–food interaction occurs because of a common pathway involving a specific isoform of cytochrome P450 — CYP3A4 — present in both the liver and the intestinal wall. Studies suggest that grapefruit juice exerts its effect primarily at the level of the intestine.4
After ingestion, a substrate contained in the grapefruit binds to the intestinal isoenzyme, impairing first-pass metabolism directly and causing a sustained decrease in CYP3A4 protein expression.5 Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours.6 The net result is inhibition of drug metabolism in the intestine and increased oral bioavailability. Because of the prolonged response, separating the intake of the drug and the juice does not prevent interference.
Individuals express CYP3A4 in different proportions, those with the highest intestinal concentration being most susceptible to grapefruit juice–drug interactions.5 An effect is seen with the whole fruit as well as its juice, so caution should be exercised with both.7 The precise chemical compound in grapefruit that causes the interaction has not been identified. There is no similar reaction with orange juice, although there is some suspicion that "sour oranges" such as the Seville variety, may have some effect.8 A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.9
There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability.3 The limitation is the individual variation in patient response. However, if the chemical that causes grapefruit's CYP3A4 inhibition is elucidated, there may be an opportunity to modulate that pathway in a controlled fashion.
What to do: Much of the data obtained on grapefruit juice–drug interactions involved measuring serum drug concentrations in small numbers of healthy volunteers. Because of the limited data and only occasional case reports,10 it is difficult to quantify the clinical significance for individual patients. One may assume that the interaction occurs primarily with oral medicines, and only with those that share the CYP3A4 metabolism pathway, with the consequence being increased oral bioavailability, higher serum drug concentrations and associated adverse effects.
Physicians should review medication lists often, with the goal of warning patients about adverse interactions. A list of medicines with which patients should not consume grapefruit is provided in Table 1.3,11,12 In the case of several medications that share the CYP3A4 metabolism pathway, but for which a clinical effect has not been elucidated or is theoretical, patients should be advised to consume grapefruit cautiously and be monitored for toxicity.
O N E
#4
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Posted 03 October 2004 - 09:34 PM
I read this stuff a while back. When I do my next cycle start with Methandrostenelone (The mighty D-Bol), I will drink a tall glass of grapefruit juice first thing in the morning. The effects of Grapefruit juice are supposed to last 24 hours.
Would be wonderful to get a 500% increase of active D-bol in the system eh?
The reason D-bol, Anadrol etc., is harsh on the liver is the 17AA aspect, which the alkylation of the 17th carbon position is what keeps the liver from metabolizing the drug on its first passes.
This could lead to the possibility of getting a much bigger bang for your 50mg of D-bol per day. If not, Grapefruit juice os good for ya anyway.
Would be wonderful to get a 500% increase of active D-bol in the system eh?
The reason D-bol, Anadrol etc., is harsh on the liver is the 17AA aspect, which the alkylation of the 17th carbon position is what keeps the liver from metabolizing the drug on its first passes.
This could lead to the possibility of getting a much bigger bang for your 50mg of D-bol per day. If not, Grapefruit juice os good for ya anyway.
#6
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Posted 04 October 2004 - 06:47 PM
doesnt hurt to give it a go. too bad i hate the taste of grapefruit. Any word on using plain grapefruit over the juice form?
Sage
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#7 Guest_Pittbull_*
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Posted 04 October 2004 - 07:59 PM
i use this with allorals and let me tell you there is a noticeable increase..
#8
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Posted 05 October 2004 - 12:17 PM
GREAT POST!!
I plan to do it, I shold be starting on MON, with my cycle.
I agree can't hurt to try it.
As as kid we would eat a grapefruit with a small teaspoon & some sugar ontop.
that had a good taste.
I wonder if the sugar will interfere in the chemical process of the GRAPEFRUIT inhibitors function?
peace
mikestrong
I plan to do it, I shold be starting on MON, with my cycle.
I agree can't hurt to try it.
As as kid we would eat a grapefruit with a small teaspoon & some sugar ontop.
that had a good taste.
I wonder if the sugar will interfere in the chemical process of the GRAPEFRUIT inhibitors function?
peace
mikestrong
#10
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Posted 28 October 2004 - 10:01 PM
Great post bro good to see some useful info.
Much Respect Big G.
Much Respect Big G.
#11
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Posted 28 October 2004 - 11:46 PM
not going to repost everything i did last time, i just dont have the time again.....but more steroid absorption is not a great thing. If you are taking what you are supposed to be taking, then take grapefruit juice to increase absorption, then that more absorption means it raises the levels to more than what you should be taking. simple as that.
#12
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Posted 30 October 2004 - 03:42 PM
GREAT KNOWLEDGE VIP TORCHY,
I will sure keep that in mind.
peace
mikestrong
I will sure keep that in mind.
peace
mikestrong
#13
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Posted 30 October 2004 - 03:44 PM
QUOTE(Torchy @ Oct 30 2004, 02:22 PM)
p.s. I forgot to mention that a guy I worked with did the above posted and it really fucked him up(kidney, liver damage due to excretion issues w/grapefruit juice and V). That's why I really jumped up on the double checking the interactions B)cool
Torchy, I am interested in hearing more about the problems your friend had. Can you elaborate on the excretion issues? Thanks.
#14
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Posted 30 October 2004 - 09:54 PM
Okay, thank you for the clarification. In your earlier post you mentioned "V", I assumed you meant Winstrol-V. That is what I was concerned about. Thank you.
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