If the multiplier is 8x at 2 hours, then isn’t cmax at least 8x? That seems useful to know compared to the rough 3X estimate I see thrown around.
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Just to hit the dead horse one more time. If you take 4mg at 2 hr and your cmax is 10. 2 or 3 weeks later you take 4 mg with GFJ and your cmax is 32.
Some would say since they took 4 mg and they got 32 in their blood then the multiplier is 8x because grape fruit juice.
Some would say without GFJ it was 10, with GFJ it was 32 so the GFJ has a multiplier of 3.2. I’m with these guys.
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Obviously this is the correct answer. But I thought that even measuring GFJ effect this way (correct one) there were results higher than 3X?
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Honestly I don’t think anyone has done it.
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Well would be interesting for guys that do blood work often to look at it this way and see what the real effect of GFJ is. As an example, I take 3+GFJ every two weeks in hopes that it is at least 3X or more. Never measured or did blood work though.
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There was a clinical trial that measured GFJ effect on Rapamycin absorption and the average boost was 3-3.5X. Although I do think there were outliers.
The original study paper is somewhere on this site.
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Thanks Chris, I meant to say that nobody here has done it. I guess with India selling Rapa so cheap GFJ probably is unnecessary, but I still think it’s a great hack. It’s a more efficient use of resources. I’m sure it is different than just Rapa, but have no way of knowing whether it’s better or worse.
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Seems most people use GFJ to increase bioavailability. Why do you prefer this over Ketoconazole which provides a very reliable 5.6 x increase? I take 2mg of Rapa about 90 minutes after taking Ketoconazole.
Ketaconazole usage can lead to liver damage
I’m not sure how big a deal the liver risk is if you’re just dosing once every week or two with ketoconazole, but I think people might avoid it for the polypharmacy issues… the more drugs and supplements you take, the greater the risk of some unforeseen interactions. I try to keep my stack as simple as possible as a general policy.
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“Obviously this is the correct answer”- but what is the question? I see two of them.
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If I take Xmg rapa with and without GFJ, what will be the difference in my rapa blood level? (answer seems to be ~3x)
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If I take Xmg rapa with GFJ, what will my rapa blood level be? (answer was ~8x for me)
Two very different, but relevant questions. I may be a little biased, as I wrote the original post, but if I could only ask one question, it would be #2.
I wonder if that will work for all values of x. Is it a linear function? We have one point.
Not saying it’s not, I just don’t know. If you increase the amount in the gut, then more will get through to the blood. Even though the units are wrong, all things may cancel out and this could work.
Does anybody know of a paper that shows blood level graphed against dose taken? You would have to wait a couple weeks between replications to let it go away.
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My reasoning for stopping ketoconazole, which, like you I loved for its reliability, was that I got the impression from my reading that its inhibition of CYP3a4 was much longer lasting than that of grapefruit, significant for a week as I recall.
Not wanting to stop for more than a day the other drugs that interacted with ketoconazole, I switched back to grapefruit. If my reasoning can be shown to be in error, I would return to ketoconazole. The connection with liver damage was never a concern given the infrequent use.
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@bicep Agetron takes 2mg with GFJ and his blood level is ~8 (4x vs. my 8x with 4mg dose).
Could be a linear function or just that day, that time, that person…
I agree with Bicep’s post - rapa is so cheap from India that GFJ is likely an unnecessary confounder. I will do a blood test with 2mg and GFJ (enquiring minds like to know!), but not today (my rapa day). I just took 8mg sirolimus from Siroboon and will get a blood test at 2 hours post dosing. I’ve been using the Biocon, but Siroboon is a little cheaper. I’ll post the results tomorrow.
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@RapAdmin Ive been squawking a lot lately about the polypharmacy issue. My issue is only my personal feeling that I was making a mistake. I completely slipped down the slippery slope of wishful thinking. I was / am addicted. But I am in recovery now. I no longer take any sleep supplements (or anything in the evening), and my sleep is already better.
I’ve cut down to 10 chemicals that I take regularly but cycle out of at least 2 days each week. I feel much safer, and I’ve shifted my focus to lifestyle interventions. I’m learning a sleep / circadian rhythm daily schedule right now.
It’s a long term plan but so far so good.
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Is it possible for the CYP3A4 inhibition to be longer than the blood levels of ketoconazole?
How long does ketoconazole stay in your system? Ketoconazole has a half-life of 2 hours in the first 10 hours of taking the drug. From that point onwards, the half-life of the drug increases to 8 hours.
Source: Ketoconazole - Side Effects, Dosage, Precautions, Uses.
If you take a irreversible inhibitor of CYP3A4, body needs around 3-4 days to recover the function cytochrome P450-3A if I remember correctly. GFJ is irreversible inhibitor, but works in intestine only.
Ketoconazole is a reversible inhibitor with very short elimination, so probably the recovery of cytochrome P450-3A must be short too.
Yes, I understand that the the time it takes for CYP3a4 to return to normal levels is not the same as the time it takes to eliminate ketoconazole from the body.
Also, the mechanism of inhibition differs between GFJ and ketoconozole and the rate of regeneration of the enzyme differs between the two…
I dont know of any study that sheds light on how long it will take to normalize the enzyme after single dose of ketoconazole. I am assuming it is at least 3 days.
I’m inclined to agree with scta123 and now expect that normalization of CYP3a4 after ketoconazole could actually be faster than with GFJ.
If that’s the case, I may prefer ketoconazole. I have plenty left, just looking for corroboration if anyone can provide it.
If the multiplier is 8x at 2 hours then the cmax is close to 8x. But that’s if. Problem is, you don’t know if the multiplier is 8x at 2 hours if you measure with or without GFJ at 2 hours because you don’t know if you’re exactly as close to the peak in both cases. Trying to measure the peak and comparing it with or without GFJ is a very inaccurate way to estimate the multiplier. It’s far better to measure at 48 hours.
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