Fwiw, because I have NO clue, I asked Claude opus and he said (I trust him as far as I can throw Dario):
Thinking through the PK from your three data points:
∙ 6mg → 2.1 ng/mL at 48h
∙ 8mg → 3.1 ng/mL at 48h
∙ 8mg → undetectable by day 6
Your apparent half-life looks like ~24–36h, which is faster than the ~62h population mean. One plausible explanation is a CYP3A4/3A5 or P-gp (ABCB1) fast-metabolizer phenotype — sirolimus is cleared primarily by CYP3A4 with P-gp efflux, and variants in either can meaningfully accelerate clearance. You haven’t been genotyped for CYP3A4/3A5 or ABCB1, so this is a hypothesis based on the observed PK, not a confirmed variant. Worth genotyping if you want to know, since it would affect dose translation for anything else CYP3A4-metabolized. Either way, it explains phenotypically why 8mg weekly is your sweet spot despite your size — you clear it quickly.
For Q2W, a reasonable starting range is 12–16mg, with 14mg as a clean midpoint. Reasoning:
∙ 16mg roughly preserves your current monthly AUC (32mg/month either way)
∙ 12mg is conservative — 75% of current monthly exposure, lower Cmax, lower GI risk
∙ 14mg splits the difference
Key PK point people sometimes miss: doubling the dose does not double the washout window. Half-life governs washout, not dose. So 16mg doesn’t wash out at day 12 just because 8mg washed out at day 6 — it washes out at roughly day 7–8 (one extra half-life). That matters for the Q2W framing: you’re buying higher peak inhibition and a longer guaranteed trough window, not “double the coverage.”
Testing plan:
1. Start at 12mg (conservative first trial)
2. Draw sirolimus at day 14, right before next dose — target <1 ng/mL to confirm true washout
3. If tolerated and trough is clean, titrate to 14mg, then 16mg on subsequent cycles
4. Optional: 48h post-dose level on the 12mg trial to verify linearity (should be ~4.6 ng/mL if PK scales)
On dosing day for RT: With your Mon RT / Wed RT / Fri Pilates schedule and an added Sat RT, Thursday dosing is mathematically optimal. It puts both Monday and Wednesday RT sessions in the deepest washout window of the cycle (96h and 144h post-dose). Saturday dosing puts Monday RT at ~48h post-dose, right near peak mTORC1 inhibition — worst timing for your heaviest session.
Caveats: higher Cmax means higher GI side-effect probability (mouth ulcers, loose stool). Watch the first cycle. And the fast-clearance phenotype is worth confirming with one more PK
I think your story makes a lot of sense. You got great newb gains on a very hefty dose of testosterone, one that pushed your levels into territory rarely seen in the wild - the true tail of the gaussian - and once you started rapa you mostly went into maintenance mode. It’s clear that 200mg/wk, when it was new to you, was effectively like a steroid cycle would be for a guy starting with more muscle mass. I experienced the same thing when I did 200mg/wk - I put on muscle incredibly fast.
Now if you’re getting stronger, you’re building muscle - the exercise science is pretty clear that neurological adaptations are short lived and only responsible for a fraction of strength gains - so once you got shredded you actually were still gaining even if it wasn’t very visible. The 200mg a week was still enough to overcome the rapa and add enough substrate to provide more strength.
But now, I suspect you’ve added so much muscle that 200mg is no longer enough to provide the anabolic stimulus that you need to grow. It’s enough to keep you in homeostasis with the rapa, though, so you’re getting the rapa upsides without the mTOR inhibition downsides. Even bodybuilders not on rapa require larger doses of test to maintain their size - some guys cruise at 600mg a week - so it seems like 200mg is now your maintenance dose rather than a growth dose. My bet is you would start to shrink, and be weaker, on 100mg/wk - the rapa would become a problem. At 300mg/wk, you’d start growing again. Not that I’m suggesting that as your next experiment or anything…
I agree… it’s actually a little bizarre. There have been short-term studies done on this (rapamycin immediate impact on muscle during training) already, so it’s not news at all. Seems like a waste of money, to be honest. It would take much longer than this study to show that rapamycin slows aging of muscle… which is what I think it likely does, but not in 13 weeks with these endpoints and this study design.
I think this study needs to be interpreted extremely cautiously and skeptical. I know the muscle protein synthesis idea exists but a mouse study already showed by using numerous doses of rapamycin during the week while exercising for multiple weeks, which should suppress muscle protein synthesis sufficiently during the intervention, that it didn’t blunt muscular adaptions (exercise capacity, muscle hypertrophy, and strength). The exercise intervention used in the Stanfield study likely had no meaningful stimulation of the mTORC1 signaling pathway given how low intensity it appears. Without any biopsy data the notion that mTORC1 was activated is purely speculative. Until a true resistance exercise study with rapamycin is performed I’d hold my tongue regarding this study with any high confidence.
"so once you got shredded you actually were still gaining even if it wasn’t very visible. The 200mg a week was still enough to overcome the rapa and add enough substrate to provide more strength.
But now, I suspect you’ve added so much muscle that 200mg is no longer enough to provide the anabolic stimulus that you need to grow. It’s enough to keep you in homeostasis with the rapa"
And, I am perfectly fine with my current muscle size and body shape right now… really has been the same for about 4-years. I think I am at my body frame’s natural-ish limits:thinking:
Certainly don’t want less muscle… but my mirror flex shows way above norm at 68 years.
If I can hover here for another decade… it would be great.
Hi, I’ve been lurking around here for a couple of years now but never posted anything because my knowledge is so limited. Reading all the posts has been an education.
I’d just like to thank everyone who posts- it’s very helpful to those of us who don’t possess the level of knowledge on the topic that so many here so eloquently express.
I’m 65 years old, female of very small build and have been taking rapamycin for approximately 3 years on and off. I sourced it from India and often wonder if it’s the real deal because I have zero side effects. Nothing at all. Nowadays I take it every 2 -3 weeks, only 2mg but with 200mg ketoconazole approximately 2 hours prior to the rapamycin dose. I figured that this regimen would give a relatively high dose without breaking the bank. Then 2-3 weeks break. As I weigh 43kg (only 150cm height)I dont want to lose any muscle (or cms!). Does anyone else worry about the authenticity of the products? Maybe I’m just not prone to side effects? TBH I would have liked one or two side effects, just to be sure that the rapa is genuine!
Anyway, thanks again for the great website and all the well-reasoned and thoughtful contributions.
I think most people don’t really experience side effects at modest doses.
What brand do you get from India?
I get Rapacan and users here have validated the brand and others. Now compounded Rapa is different and the US sellers that sell this are pretty upfront about that.
As you probably know, ketoconazole is probably a bigger variable than a branded India source of Rapa. Yes, it will raise levels but how much is the variable.
I think very few people think Rapa will cause loss of functioning muscle mass. Blunting growth is expected depending on dose - even before these results. But actual loss, besides some beneficial autophagy, is not expected.
Now everyone has loss from time to time and you need growth to replace it. So that is an issue. I think a low muscle mass woman should be working hard to increase mass. And you presumably know that is muscle stress, protein, some calorie excess and testosterone and preferably in the absence of Rapa. Which means that you likely should keep your Rapa intervals on the longer side.
As a male, I can probably keep intervals tighter. My muscle mass is not likely to be a life limiting factor.
I would not think 2mg every 2-3 weeks would have much of an effect. It is a bit like the PEARL trial conclusions … viz if you don’t take much rapamycin not much happens.
Thank you for your reply. I know it’s a very low dose but because I also take ketoconazole 200 mg with it this should greatly up the blood levels of rapamycin. If both drugs are fake then I’ve been wasting my time and money - which is quite likely unfortunately!
Thanks so much for your reply, David. Very helpful. Yes, I am getting rapacan too, so that’s good news to know that it’s the real deal. The man in India seemed very good, but of course you just don’t know when buying medication online. We are very much warned against it here in Australia but, like most people around the world, we Aussies ignore the authorities - unless we really are convinced that they are on the right track!
That has been a rough estimate based on quite a bit of data; however, I’ve mostly stopped doing the multiple levels required to hunt this down and taken the approach of getting a level of 3 ng/mL at ~30-35% of the dosing interval, such that we know the level is above this for approximately 1/3rd of the week.
I can speak to the safety of this approach, but none of us can speak to the efficacy. However, the dosing is almost always higher than what individuals used to take when the approach was a 5 or 6 mg per 7 days. My average dose remains very close to 0.1 mg/kg when dosed every 7 days without GFJ. However, I have individuals requiring <0.05 mg/kg and some at 0.3 mg/kg … so a 6 fold difference to achieve a similar target.
Single dose half lives like what I’m testing do seem to be significantly shorter than the half life documented on daily dosing. I’m however unable to find decent documentation in the literature available on this; but there isn’t much documentation on cyclic dosing and levels.
I think you need to focus moreso on how this actually works. I am not persuaded that increased frequency has any particular benefit beyond reducing the side effects of higher dosing.
@DrFraser
I’ll say this out loud to make sure I understood you correctly.
If we switch from 7 to every 14 days, you still look for a level of 3 ng/ml at 30-35% of the interval.
That means I’d have labs drawn aprox 4.6 days after dosing, and I’d want the result to be 3 ng/ml.
Not medical advice of course, but what might be a good generalized formula to use so we can have an educated guess for what our 14 day dose should be? Through testing, I know 8mg is my 7 day dose. Claude suggested I try 12mg and then work up to 14 (or even 16, but that sounds intimidating). Does that sound reasonable?
I would follow that up with labs, and then how to tinker with the dose should be fairly obvious.
And yes @John_Hemming, I prefer weekly for that very reason. The idea of having side effects makes me a little wary about this trial… but if it might be better for body composition, sigh, I guess I’ll try
