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Grapefruit Juice and Orals
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Grapefruit Juice and Orals - 03-15-2005, 10:33 PM

Hey Bro's here's a question for you. Do any of you know if grapefruit juice should be avoided while taking orals? I know some perscription drugs (Lipitor for example) are not to be used with grapefruit juice as it can caus too much of the drug to get into the liver. Just wondering if any oral gear is the same.


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03-16-2005, 07:55 AM

Punchier Drugs--With Grapefruit Juice
A glass of grapefruit juice not only helps the pill go down, it also makes it more potent. Now, a study in the current Journal of Clinical Investigation has revealed why: A substance in the juice fights a drug-degrading enzyme in the intestine. The insight could be a first step toward increasing the effectiveness of some oral drugs.
About 3 years ago, researchers noted that grapefruit juice helps the body absorb many types of drugs, including sedatives, hormones, and protease inhibitors. A group of doctors from the University of Michigan and the London Health Sciences Centre, in London, Ontario, set out to investigate. They focused on an enzyme in the liver and intestine, called CYP3A4, that usually breaks down toxins from spoiled food. "It's [also] the most prolific of the drug-degrading enzymes," says Paul Watkins, a member of the Michigan team. In fact, it contributes to the breakdown of about half of all known human drugs.
Watkins and his colleagues gave felodipine, a calcium channel blocker used to control high blood pressure, to 10 healthy men, both with and without grapefruit juice. The grapefruit juice increased blood concentrations of felodipine more than fourfold. The team also measured the concentrations of CYP3A4 levels in the intestine and found that they fell by 62%. Something in grapefruit juice appears to be blocking the action of CYP3A4. But the concentration of CYP3A4 in the liver was unchanged--suggesting that the juice does not affect the rate at which the drug is metabolized once it enters the bloodstream.
If the active ingredient of grapefruit juice can be identified and isolated, drugs might be made more effective--and less expensive per useful dose. Adding grapefruit's CYP3A4 blocker to a pill could also assure a set dosage, an advantage, because people naturally vary 10-fold in how much of a drug they absorb. "It will make a lot of difference in the way people take drugs," predicts Raymond Woosley, a pharmacologist at Georgetown University Medical Center


Don't ask me where to get the stuff....I'm still trying to find that part out!


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03-16-2005, 09:11 AM

I think the danger might also be that the 17-alpha and methalated substance might be more toxic to the liver. I'll do some more investigating as well.


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03-16-2005, 11:18 AM

Here's some research for you:

Drink 250ml of grapefruit juice (thats 8.4 ounces) with your oral steroids, and you just need to drink it once per day, even if you take your orals spread out throughout the day. I've seen studies where absorbtion of some drugs was increased by up to 500%!
Also...before you ask about the effects of grapefruit juice on oral rec drugs the answer is YES, this applies to ALL ORAL MEDICATIONS/DRUGS.

Here's the whole article.

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. Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours. 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. An effect is seen with the whole fruit as well as its juice, so caution should be exercised with both. 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. A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.

There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability. 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, 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. 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
   
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03-16-2005, 04:30 PM

Thanks Oracle. I don't take any oral rec drugs, so that isn't an issue.


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03-16-2005, 06:49 PM

Quote:
Originally Posted by Freejay
Thanks Oracle. I don't take any oral rec drugs, so that isn't an issue.
Yeah that's good....but the first paragraph should help you out as far as gear goes.
   
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