Exactly… why if I do use GFJ… I squeeze 1 fresh Red Grapefruit… makes about 5 fluid ounces and drink it with the dose… and I get a 6x’s multiplication of my rapamycin dose.
Been on Rapamycin 2 1/2 years. Pretty much no extra fat anywhere. So maybe I get a bigger kick.
Great link - thanks for sharing. I think this can be helpful to everyone here.
Can you share what the exact protocol you applied to determine your rapamycin half-life? At what times did you do your blood tests?
Sure, some of it was noted on the half-life worksheet, but in summary:
Think that covers it, but lmk if you have any other questions.
Now, want to figure out what potential maximum dose will inhibit mTORC1, but recede quick enough in the blood to not inhibit mTORC2. (Vaguely recall reading anywhere from 5 days to over a week before mTORC2 gets impacted?) Also, does a little mTORC2 inhibition (at least intermittently) provide added benefit, since it’s involved with proliferation, and insulin signaling (though inhibited immune cell proliferation might not always be a good thing)? Furthermore, how long of a trough level is necessary for mTORC2 to adequately replenish itself?
So much still to discover, so thanks for your contributions so far…your help and oversight are much appreciated…UB.
Thank you for the tip on Marek Health! I had no trouble placing three orders (each about 12 hours apart), and while it said receiving the lab slip could take a couple of days each one was available within a few hours of my placing the order.
I’ll update this post if I can figure out a spreadsheet to share, or maybe someone else is better at Excel than I am and can create one. I did a series of blood draws over three days, each at about the same time (blood draws were within 10 minutes of each other - one day apart). My goal was to see how much of an impact eating a whole grapefruit might have on me and also how fast my clearance was. Here are the results:
Day zero, -2 hours: 2mg tablet of US prescribed/US pharmacy generic sirolimus followed immediately by eating a red grapefruit. I was otherwise in a fasted state - I’d done a set of routine safety labs (fasted) earlier in the day, so this was rapamycin on an empty stomach followed immediately by a whole ruby grapefruit.
Day zero: 8.1 ng/mL (I assume this is pretty close to peak)
Day one: 2.3 ng/mL (this is MUCH lower than I expected - presumably it should have been ~5.3)
Day two: 1.8 ng/mL (this seems more in line as a correct half life relative to day one’s value)
My BSA is just shy of 2m^2 (thanks @59vw for posting this link in another thread: BSA Calculator - Body Surface Area). Conveniently for me, it looks like I’m approximately the same “size” as all of the subjects in the Sirolimus Kinetics and Safety in Volunteers paper.
Any thoughts?
I’m interested in repeating the same round of tests in a couple of weeks, this time just consuming 2mg (no grapefruit) and also taking at least one additional draw (day three). From this thread (Rapamycin / Sirolimus Blood Test - My Results - #43 by RapAdmin), @RapAdmin mentions it may take 1-2 hours for grapefruit to reach its peak. So, one additional thing I could try is eating the grapefruit at t-4 hours, then having the rapamycin at t-2 hours, then doing the first blood test at 0 hours. Another thing I could do is skip the grapefruit variable, bring a book, and hang out at the phlebotomist for a couple of hours - maybe doing a draw at 30, 60, 90, and 120 mins.
Also, in looking at the charts from the above paper (specifically Table 3 and Figure 1) it seems like my assumed/near peak at 2 hours more closely maps to a somewhere between a 0.3mg/m^2 (0.6mg dose equivalent) and 1mg/m^2 (2mg dose equivalent). I.e., either the whole grapefruit did nothing, or it did something but my body just doesn’t respond to rapamycin much. And, also from Table 3, it looks like tmax was reached at sub one hour across all subjects (roughly an average of 45 minutes). It’s hard to see from Figure 1 how fast the initial fall off is. I’ll see if I can find their underlying data.
see my testing journey in this other thread:
Did anyone test their rapa level in uk? I found a self referral lab in London that will do it, not very cheap but I will survive it for two tests. Just wonder if they make any fuss asking why we take rapamycin…
I don’t think the labs care what you test for as long as you pay.
I’ve used DocTap in London for some of the more unusual tests and the person I saw was just very interested in everything I was doing in respect to my health.
I found out that I can get “K-Sirolimus” test quite easly at my local clinic. It does not cost that much (30 EUR) and they are willing to take two samples of blood and test both for the same price, one before taking rapamycin to test trough values and the second one hour later to test the peak values (cMax).
I am not really sure at the target values. What would be a good trough value that would show that my MTORC2 is not inhibited? would trough value < 1 ng/ml be good or would you aim for even lower? like < 0,5 ng/ml…
What is the peak (cMax) value I should aim for? Or what do you thing it is a good peak value? @Agetron did you test your peak when taking 6mg without GFJ? Do you have results from you 2mg with GFJ? Did any of you do the test? I am taking pfizer rapamune 5mg weekly (is there any reason to expect rapamune would give me a better peak than any generics?) and what would be a good peak (cMax) target for 5 mg? In the GFJ/ketoconazole study the mean peak value (cMax) for 5mg was 25,8 ng/ml (but 6mg was only 15,0 so it is not really precise science). Would you go with this as an orientation? Test offered in the clinic does not have any reference values…
Wow that is a great deal two for and a low price. I pay $95 US… each test… about $200 total.
I would say from most on here and myself… a trough of 1 or less shows you have gone down low enough not to inhibit MTOR2 the previous days.
My last trough was .7… less than 1.
My phlebotomist… messed up my vials and didn’t send the lavender topped one… so no trough… assuming it was .7 or around there.
I hope they didn’t mess up my post dose draw. Going to see my physician for my blood screening review… at 11am. Will find out then… might need to redo it all tomorrow at day 7 of my last dose.
Will report back after my meeting.
I understand how you calculate the half-life. But how are you coming to the conclusion that your absorption is particularly low relative to others? Are you comparing it to the figure in PMID: 11034258 that is posted in the first post in this thread?
I was thinking it’s good to compare blood levels to those in PMID:11034258 to get a comparison to how your levels are similar to the people in the study. That could give an estimate of whether you absorb more or less than average. However I wonder if it is comparable if you take a different type of rapamycin formula. In PMID: 11034258 they administered aqueous solutions containing rapamycin. That’s not the same as giving rapamune pills. It’s more similar to taking rapamycin powder in water. So I wonder if it’s comparable to the same dose taken as a pill. I say this because some people have said on this forum that rapamycin taken as a powder has worse absorption than rapamune pills. Apparently rapamune contains rapamycin complexed with hydroxypropyl betadex which protects it somewhat from stomach acid, If that’s true then the figure in PMID: 11034258 isn’t really useful in figuring out whether one has high or low absorption relative to other people. Am I missing something here?
The figure in this study (the one in the first post of this thread) is the only good one I have seen that gives a good idea of the levels of rapamycin in the blood at different times after different doses. Unfortunately the levels are for sirolimus in aqueous solution which may not be comparable in bioavailability to rapamune pills so for people wanting to test their bioavailability with rapamune pills this study doesn’t help much. So those taking blood tests after taking rapamune pills can only figure out roughly how fast they metabolize it relative to others (by the half-life) but not how much they are absorbing relative to others. That’s unfortunate because the latter is even more important.
Given the above, I have a suggestion. Once more people have taken blood tests of rapamycin after intake of rapamune, it would be good to create a database or graph that shows the dose (in mg/kg bodyweight) each person took, the gender, and the blood levels at whatever time points they measured. Once sufficient number of people have tested their levels that way we would have a database with average levels to which people can compare to see if they absorb relatively much or little. This is greatly needed since the bioavailability differs by quite a lot between people. We really need to encourage more people to test their levels and report them along with the relevant data.
Thanks, I used it this morning and will test after my next dose to see how effective my protocol is.
Relative to what I said above. All we need to get a rough idea of the average absorption of rapamycin is for at least 10 people to measure their rapamycin levels at say 24 or 48 hours after rapamune dosing (after not having taken any for two weeks prior so their levels are zero before the dose). Measuring close to the peak level would not be good because it will vary widely depending on the exact timing but at 24 or 48 hours would give a good data for comparison.
I think this can give rough idea of cMax values per different mg as it compares it taken with ketoconazole or without on a sample of 2-6 people and uses sirolimus pills (GFJ study uses oral solution).
The pharmacokinetics of sirolimus study (done on several hundred patients) shows fast absorption and reaching maximum blood serum concentration in 1-2 hours.
Hi, I posted in the wrong thread. Here is the link to my post about my experience testing sirolimus blood levels:
Considering above data I posted, 30 ng/ml is a an expected maximum serum concentration (1-2h after dosing) at 6mg rapamycin (especially if you take it with fat, which in my understanding will give you some boosting of bioavailability).
I would also test trough levels too (just before your next dose) as you want this level to be almost zero not to suppress MTORC2 too much/all the time.
Thanks for that information. Very helpful. What is the source?
This seems to be the source: Phase 1 Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients - PMC
Yes, this is the study I used. In what I could find this is the only study that can be used to determine a tMax from a single dose, other studies were done in transplant patients with completely different dosing regimens…
