I’m a healthy 50 year old man taking 3mg/week and I take it with grapefruit juice.
I’m currently taking a compounded version, but I plan to move to a non-compounded version (like Rapamune) asap. I’m aware of the speculation that the compounded version may have less bioavailability, which is why I’m taking it with GFJ.
I plan to do multiple blood tests in order to see what’s actually happening.
I plan to test the sirolimus level in my blood after taking my weekly dose. I plan to do at least these tests…
blood test after taking the compounded version with no GFJ
the same as above, but with Rapamune
either the compounded version, or Rapamune but with GFJ (I’m not sure yet…we’ll see).
In the formal study that tests the bioavailability increase when sirolimus is taken with GFJ, there is a good graph showing that blood levels spike in the hours after taking it and then it levels out while in steady decline.
I was thinking I would do the blood test 2 days (48 hours) after dosing - but I don’t have a strong view. 3 days?
At first I was thinking I would do the blood test 2 or 3 hours after dosing, but given the high volatility of the drug in my bloodstream during that time, I think it’s not ideal.
With all that said, if anyone has any thoughts about how long after dosing I should do the bloodtest, please share. Also, I’ll be at a Labcorp (I think), so I may not have total control as the the minute my blood is drawn…
Testing it 48 hours after dosing is a great idea. I would do that.
Note that many people here have tested their rapamycin levels a few hours after dosing but I don’t think that makes any sense, other than for the purpose of seeing if whatever you’re taking actually contains rapamycin. Testing in the first 12 hours after dosing is kind of pointless since levels go up so fast in the first hours and drop so much thereafter and there is no way to know how close you are to the peak. Therefore any comparison between such measurements is practically useless. After 24 hours levels will have stabilized mostly so I suggest testing at least 24 hours after dosing. 48 hours would be even better IMO. If you want to calculate your half-life then testing at 48 hours and then either 96 or 120 hours would be good. Anyway, please post your blood test results after doing the tests.
I did a test after 24 hours. I took 6mg with GFJ (2 hours earlier). My result is 3.2 ng/L which I think is on the low side. I’m going to redo the test next week. But at 2 hours after taking rapamycin.
I think testing 48 hours after dosing is a v. good idea. So much variation in the results if you are testing in the hours around dosing leading to unnecessary worry from people about the rapamycin they bought being under-dosed/ineffective for them.
Other people on this site with more experience with regularly testing blood sirolimus levels may have a different perspective though especially if they are focused on peak levels.
It’s almost certainly going to be a lot higher at 2 hours after taking rapamycin so I don’t see much point in testing that. Why not do a retest at 24 hours with no GFJ or more GFJ, then you’ll see if the GFJ is doing much. Your level of 3.2 is kind of low with GFJ but is not so if it were without GFJ. So one possibility here is that GFJ isn’t having much of an effect on you personally. If true the dose of GFJ might not be high enough for you. How much GFJ did you take?
But yes, I agree with ReppinMycin above when he said testing at 48 hours is better since there is less variation if you test earlier. 24 hours is ok but there is less variation if you test at 48 hours so that would be a more accurate time point to test.
If you look at the graph the decay is very fast. At 24 hours it is almost impossible to estimate your initial dosage. At 48 hours it will flat line even more. Anyway I’ll test it again next week with a higher dosage. Maybe 10mg with GFJ.
You need to consider the effect of the GFJ. GFJ doesn’t have a standardized multiplier effect. It not only differs between people but also depending on the dose. A high dose of it might cause a 4x multiplier effect in one person while a lower dose would cause almost no increase in that same person. People really are shooting in the dark with GFJ if they don’t test how much of an effect it is having.
Perhaps I’ll do it without GFJ the next time with 6mg. That is the only way I’ll know if the GFJ is working. Or I can start by testing them 2 hours after. I know they are working because I have some minor side effects.
I see. Yes, if you have side effects when taking it with GFJ but not without GFJ then that would be a strong indication that it’s increasing the rapamycin concentrations in your blood by a good bit.
The source of GFJ can also matter. Type of grapefruit, fruit vs juice, etc. Also the time between GFJ consumption and rapa dose can matter. Search for details on this site.
Unless human clinical data eventually says otherwise, design your dosing schedule to avoid inhibiting mTORC2. You’ll need some personal data points to assist with that. A peak rapamycin level of 10 ng/mL probably avoids inhibiting mTORC2.
Get three sirolimus/rapamycin blood tests : 3 hours after your dose (~peak), 7 days after your dose (potential trough), and 14 days after your dose (confirming the trough).
Design your dosing schedule based on the levels you see at 7 days and 14 days. Based on rapamycin’s half-life, I expect most people to have detectable levels at 7 days. I suspect that matters less for lower doses, as the ng/mL amount of rapamycin would likely be below the mTORC2 inhibition threshold. But for higher doses, 14 days is probably wiser. But personal blood work is necessary to determine those parameters.
I’m not currently aware of studies that provide significant insight on the duration of a “rapamycin vacation”. In female C57BL/6NCr mice, 15-months of intraperitoneal injection with 1.5 mg/kg rapamycin, 3 times a week every other week, resulted in sustained mTOR suppression in the heart when measured 13 days after the last dose (Leontieva et al. 2014). The same dose given orally did not have that effect. So, either 13 days was sufficient to restore normal mTOR signaling in mice—or that dose never substantially lowered it to begin with. If anyone is familiar with studies that could shed light on the duration of a dosage break, please join in. As it stands, I don’t think mTORC2 signaling would present an argument for breaks longer than two weeks. But it may turn out to help reduce rapamycin’s other side-effects (e.g. hyperlipidemia). In that case, personal blood work to monitor ApoB would help direct the frequency and duration of rapamycin breaks.
Currently, I prefer an alternating schedule with rapamycin (Week 1), 24-36 hour fast (Week 2), rapamycin (Week 3), 24-36 hour fast (Week 4), break (Week 5), then repeat. But I will update and tweak that based on 1) new evidence and 2) my own blood work.
I didn’t intend to spend the morning writing this, but there you have it! We do not have definitive answers, but we’re miles and miles ahead of having nothing to go on. Bottom Line: We know enough to design more and less rational dosing schedules.
Correct me if I’m wrong. A normal person who doesn’t take sirolimus will not have any reading on the blood test right? And after 14 days it should pretty much be very low like 0.2 ug/L?
What is a good target ug/L after 3 hours and 7 days?
I’m going to be doing weekly test until I get this sorted out. Thx