Rapamycin pharmacokinetics model

@Brimstone Heres what I do. The edema thing is something I experienced from a higher rapa dose and with experiments with a lot of citrate (sodium / calcium / magnesium/ potassium). I’ve given up both.

I weight 200 lbs

  • if I am sick or feel something coming, I skip my dose
  • if I have an infection (boil, etc), I skip a dose
  • if I am feeling beat down for any reason, I skip a dose
  • I take Rapa every 14 days, and after 28 days I take an extra 7 days off (using this approach I do not get infections and almost never get sick)
  • 4mg rapa plus gfj (3 grapefruit: ~10-12 hours before / 6 hours before / 2 hours before l)
  • no food beside gfj for 12 hours before and after (this is for body fat control. I also hope for a higher peak and lower AUC for rapa but I’m told this doesn’t happen)
  • I skip all my meds and supplements for the rapa day and day after. I add metformin ER for the 24 hours before and after my rapa dose
  • I stop weight lifting for 36 hours before rapa (to recover), and then avoid lifting for at least 24 hours after depending on soreness. I ride my bike for an hour a day on these days.
  • I eat low protein for 24 hours before rapa, and for 24 hours after rapa. This is especially true during the GF fast.
  • I was taking Rapa in late afternoon to get tired before bed, and then sleep it off. That works well. I just started doing a moderate intensity 1.5 hour bike ride starting an hour after taking Rapa. So far the result has been no muscle soreness and no fatigue at all on the second day. I like this better so I’m switching to this.

Hope that helps. You should know that I am not a doctor and I essentially have no idea what I’m doing with rapa. As far as I can tell, no one can tell anyone else what will work until they try it and see what happens. Be conservative. Take your time. Don’t get emotionally attached. “Mind like water” (from a podcast I’m publishing tomorrow).

Good luck

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One of the things to watch out for in structural mathematical modeling is trying to estimate too many parameters with too few data points. In this case, you are trying to estimate 5 parameters, so you would need a set of time points along the PK curve such as these authors used for sirolumus: Blood samples were collected onto sodium edetate for determination of sirolimus in plasma and whole blood, before administration and at 0.33, 0.66, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144, and 312 hours after administration of sirolimus or placebo. (Brattstrom C et al Therapeutic Drug Monitoring 22:537–544; 2000) They employed Non-compartmental analysis, which makes fewer assumptions than a compartmental analysis. With enough time points, the parameters resulting in best model fit are determined by the model run minimizing the error or difference if you will between the predicted and observed time points.

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Looks like the high fat version slows down the peak so that there is enough point to fit a Michaelis-Menten model. I use a non linear optimizer to find the k coefficients giving the best fit and it works quite well.

Here is the latest fit:

Zoomed on the peak:

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[Disclaimer for those who skipped the discussion above, The data for this model comes from a paper and obviously individuals will have variations in term of absorption, distribution and clearance compared to that]

Comparing 1x 6mg vs 2x 3mg, 3x 2mg or 6x 1mg spaced 24h:

Here is the distribution to the average organs:

I would say it’s probably better to stay on a 1x 6mg schedule unless people want to avoid an initial higher peak.
BTW the other ones are still high after 1 week.

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Very helpful thanks. Just to clarify, you take 4 mg of Rapa every 14 days? Then after 28 days you take 7 extra days? So, it’s 2 doses in 35 days? I just was to make sure I’m reading it right.

My current methodology is 6 mg weekly for 2 months, then I take a month off. I take 100 mg acarbose with every meal and take 100 mg canagliflozin daily. To your point, I have no idea if this is effective or not, but I can tell you that my blood tests are typically very good on all parameters. Like you, I rarely, if ever, get sick. The only difference I see is that Rapa gives me an almost euphoric like high and gives me energy. I have to take it in the morning because at night it would make sleep impossible.

And, I completely understand that we are all winging it and that you aren’t a doctor, but I appreciate that disclaimer. LOL.

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Yes, that is correct but it’s 4mg with gfj. Call it 12mg. We are all winging it. I am very cautious about getting addicted to it and being reluctant to miss a dose. I’ll skip a dose for many reasons. I have tried higher doses and more frequent doses. This pattern feels the best to me.

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I’ve never experienced anything like that, I gotta microdose some golden teacher to get that :slight_smile:

Moving this to my results thread instead: Blood concentration of rapamycin (N of 1 dosage, model and biomarkers) - #4 by cl-user