i read somewhere on the internet a scientific study with measurements etc. and they were using 400mg - i think it was like 200mg sometime prior and maybe another 200mg after but don’t remember exactly
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I just took one pill on a full stomach, and 10mg rapamycin 10 mins after
“Mean peak plasma concentrations of approximately 3.5 μg/mL are reached within 1 to 2 hours, following oral administration of a single 200 mg dose taken with a meal.”
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I just took one pill (200 mg), and 20mg rapamycin at the same time
Seriously ? That’s sounds like a dangerous dose Alex
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Get ready for diarrhea & GI issues… But seriously, please post any positive or negative effects over time that you notice.
I don’t think its dangerous as a single dose - I wouldn’t keep it up over a short period of time (i.e. multiple doses over a few weeks is likely more dangerous). Details on safety: How Safe is Rapamycin (part 2)
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If you get full effect of the ketoconazole, you realize thats equivalent to over 100mg rapamycin?
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If you want the full effect of Ketoconazole, you should wait 2 hours after taking it to then take Rapamycin. Since you took them simultaneously, the effect will be less than the expected 5x, I would think. Which, considering the 20mg, is probably good.
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If you want similar absorption try GFJ + Metformin + EVOO.
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Since you use ketoconazole, I wonder if you have considered using Ritonavir. I have not yet used any of them, but I like to have a more précis CYP3A4 inhibition than I probably get from Grape fruit. So I consider taking Ritonavir instead of GFJ/GF. But I would like to hear more about how it affects people taking it intermittently, and if there are any potential side effects when used only intermittently.
The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism? - PubMed (nih.gov)
DeStrider, how much 1g of Metformin affects absorption of Rapamycin?
I take Metformin 1g every second day, on my rest day, I work out one day, other day Metformin etc.
Do you take Metformin the same day, how do u take it in relation to Rapamycin?
Unfortunately I do not know how much Metformin affects Rapamycin absorption. I take it one hour before I dose as it has a similar affect as GFJ in neutralising the enzymes that break down Rapamycin.
Alex, your bold simultaneous ingestion of rapamycin and ketoconazole has certainly sparked interest. Thank you for sharing your experiences.
I don’t know if you did, but I hope you did, follow up blood testing. It could be valuable if those of us using ketoconazole would post blood concentrations and time after ingestion for different dosing and different intervals between the keto and rapa.
For example, on 4/18/23 I got tested at 90 minutes after 6mg rapa. And my rapa was 90 minutes after 200mg ketoconazole and was taken with breakfast. Sirolimus concentration as measured by Marek Health was found to be 81.3 ng/ml.
I come up with a rough estimate that my 6 mg dose was comparable to 35 mg rapa alone.
My estimate is based on comparisons with tables in the following studies: Phase 1 Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients - PMC ,
Of course there are significant differences in absorption rates, so individual results may vary.
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If someone can help fund my blood testing after my N=1, I’d be open to it (I can disclose all, I’m unsure about the costs of testing just sirolimus [plus finding the phlebotomist from quest]). I’m willing to try again (even 30mg + keto next time). I am heading to zuzalu now
PayPal/zelle is simfish@Gmail.com
FYI - I don’t feel anything different after the mega-dose. I know there’s a placebo effect where I feel like my body got “cleansed” due to the increased autophagy (which could be true or could be placebo)
I have very pronounced ADHD-PI, so I have more experience with accidental overdoses than many (though I at least never overdose on adderall 
)
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Anyone has any idea how ritonavir effects absorption of rapamycin? If you compare it with GFJ or ketoconazole… Anyone tried it? From this study seems that it would give you 7 fold absorption if my diagonal reading is correct. This could mean 1 mg of rapamycin would be enough once per week. Ritonavir is commonly available in Europe and much easier to get by as ketokonazole and also very reasonably priced (around 0,7 eur / 100 mg pill)… probably pulsed dosing of ritonavir wouldn’t be problematic and side effects minimal?
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Especially the increase in AUC, is impressive.
“The 3D regimen was administered for additional days after the co‐administration of sirolimus (Days 16 to 34 in Period 2) or everolimus (Days 16 to 28 in Period 2) to maintain inhibition of CYP3A‐mediated metabolism and to allow adequate characterization of the terminal elimination phase for determination of the half‐life of sirolimus or everolimus in the presence of the continued CYP3A inhibition.”
“The results of the present study showed that multiple doses of the 3D regimen resulted in substantial increases in the exposure of single‐dose sirolimus and everolimus. Sirolimus dose‐normalized Cmax, t 1/2, and dose‐normalized AUCinf increased to 6.4‐fold, 2.6‐fold, and 38‐fold, respectively. Everolimus Cmax, t 1/2, and AUCinf increased to 4.7‐fold, 2.8‐fold, and 27‐fold, respectively. It is worth‐noting that the increases in AUCinf across individual subjects ranged from 19‐ to 61‐fold for sirolimus, and from 20‐ to 36‐fold for everolimus.”
They kept giving the subjects the CYP3A4 inhibitors in the days that followed the sirolimus. But besides that, the Cmax is also impressive. Ritonavir is a very well know substance with millons of users.
it would be interesting to see Ritonavir’s effect on Cmax, when given only given intermittently (to boost Cmax.) Ritonavir is very potent CYP3A4 inhibitor so please be careful if you decide to try it. Personally, I wait until I have learned more from present users of Ritonavir. There are quite many.
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Do you know anyone that takes it pulsed/intermittently together with rapamycin?
I was up to a personal experiment… I was hoping I can get my rapamycin levels measured (trough and Cmax) on several different combinations since I can get the test relatively well priced at the local hospital. Maybe I can get hold of ritonavir and try it too.
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If you’re going to inhibit 3A4 in the liver with drugs (unlike grapefruit, which mainly just inhibits 3A4 in the intestines and affects absorption only, not metabolism/elimination), you’re going to slow down elimination of the rapamycin and therefore prolong its effects. Is that really what we want? Isn’t the whole purpose of weekly or biweekly ingestion to spike rapa levels for a couple/few days and then have a period with low or zero levels? Otherwise, you might as well just take it daily and have all the resulting side effects and downsides that transplant patients have.
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Ketoconazole and ritonavir indeed inhibit CYP3A4 in liver as well, but this is only effective if you take it prolonged with pulsed doses or rapamycin that way they extend the rapamycin half life too not just absorption. If you take it only shortly before rapamycin the effect in liver should be negligible. Ketoconazole half life is a bit complicated but first half life is two hours, half lives after that are a bit longer but still it is measured in hours, ritonavir half life is 3-4 hours.
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