#21

:+1: I’d still go for Grapefruit juice to boost my dose :sweat_smile:

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#22

I get it when traveling personally or friends/patients go over to turkey. Can’t have it sent, it won’t go through customs.

#23

Yes, there are some things still unclear and yes, my wife also gave me the name “labratory mouse” for that and she’s absolutely right.

Because of the unknown stuff I just decided to give me some extra days for washout in my dosing regime.
There are some reasons that kept me off ritonavir for a while:
a) lowered uptake of orally administered vitamines such as B12 and D3 and so on
b) I have a relatively strict diet plan for longevity propose that is far away from the DGE (like FDA)-believes for what is good for me and I am acutally sure that it will interact in some ways with CYP3A
c) I already eat lots of foods which inhibit CYP3A4 (i.E. Goji Berries)

on the other hand I have a relatively white skin so I am actually sensitive to the sun. I tried furanocoumarines first as I wrote but it wasn’t an option for the long term.

But I have no concerns on a high AUC. Seems at least for me that a high AUC is beneficial. So i decided to take ritonavir with a safety washout period.
I’ve also checked some blood markers (some=6 pages) and they are all going into the right direction. So I think I am on the safe side. But I think of doing the next blood count without my medical just to test all the markers I really want to have, including sirolimus. Is there something I need to know if I would send my blood to a lab?
If it is possible for me as a non m.d., I can answer your first question a little bit better. :wink:

I also ordered twice from turkey over a ‘trader’ who sends from within the EU (link is somethere here in the forum, search the ordering from turkey thread). Its ~3,50€ per Pill.
I also tried importing S as pure substance or as pills as a company. No way.

If I was from austria or switzerland, I just would travel to slovenia to buy me large amounts of S in the local pharmacys. I think it’s ~2€ per Pill. S is relativley cheap in east & south-east european countries, such as slovenia, slovakia and so on.
Cheapest legal source close by for me is a pharmacy in the netherlands. 4€ per pill. 4,50€ if ordered online (to germany).

Regarding the number of papers on ritonavir, found that remarkable too… seems like the pharma industry dosn’t care about if a drug is widely used or not, but the price seems to matter. On the other hand it seems that the first class of HIV pharmaceuticals aren’t an option anymore for HIV-patients.

#24

Thanks for the comments & info about Turkey and Slovenia. In terms of cost, it just seems difficult to get it cheaply in Europe. So if I ever come to Slovenia, I’ll have a look at the pharmacy there, preferably in combination with a vacation

Sirolimus seems to be less toxic acutely, but I would still have great respect for a chronic overdose. It may be that a certain blockade prolongs autophagy and thus perhaps health or lifespan. However, mTORC1 has vital functions (nerve cells, insulin metabolism, glucose metabolism, muscles, immune system), otherwise it would not have been conserved across several species.

In this respect, excessive inhibition does not seem desirable. I have also seen patients with substantial immunosuppression and bacterial infections under relatively low daily doses of mTor inhibitors.

With regard to blood tests, a lipid panel, HOMA index and a small blood count might be useful with sirolimus.

Level measurements (Sirolimus) are common, but only validated for daily dosing. In this case, a trough level would be taken after a few days to ensure that it is within the defined target range for immunosuppression. At most, you could take a trough level a few days after taking it to see that it is not in the toxic range, but it shouldn’t be if you take it responsibly. AUC is very cumbersome and expensive to measure (several blood draws necessary)

Perhaps colleagues who frequently prescribe this for our purposes have other suggestions, but in general it is often the case in medicine that more measurements don`t necessarily bring more benefits

#25

I’ve checked lipids twice and full blood count once near my rapa intake.
In short: its fantastic. Blood glucose is at normal level, hba1c is fine but because of my diet it should have been lower.
it is maybe due to the sirolimus intake.

If the exact levels are interessting for you, I’ll add them in here but I don’t think that it is neccesary to check them again.
The last checkup was due to some issues at the nephrology. I asked them to check sirolimus blood levels but they refused to check off label taken drugs. Next time I’ll try it again with a referral. I don’t know yet how often they will check sirolimus blood levels, I only know they will. :wink:

my idea is to check them at day 4 after intake (exactly 96h after intake). It should be possible to extrapolate the curve from that point on. Don’t you think?

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#26

That’s good news about your blood values! Are you following a special diet if you suspect your HbA1C should be lower? Did you have this and the lipids checked before taking sirolimus?
I’m still skeptical about sirolimus levels: maybe it makes sense to check that you’re not in a rather toxic range, but we don’t have any reference values for non-daily doses. There are only reference values for organ transplant patients, but at around 4-12 (20) ng/dL (through, i.e. directly before the next administration) they have a significant immunosuppression. You should certainly not be above that. However, this raises the question of when to measure when taking weekly or biweekly doses? The half-life is long (several days) so it could be that 96 hours after taking it is a good time…The way I see it, one cannot extrapolate AUC from just one value.
As I understand it, you can’t extrapolate AUC from just one value. But I’m not a pharmacologist… But even if we could determine the AUC we wouldn’t know what value we want to reach…

#27

lipids:
I dont have enough data to be absolutley sure about this. My lipids tend to be more or less stable (=within a really health range)

My diet is a more or less vegan whole food diet. I included fish (esp. sardines) as well after some months on a completely vegan diet because my blood markers didn’t show any improvments (lesser triglycerides, okay, but that’s only the whole count for triglycerides, specific trigylcerides wern’t listed)

Diet:
200-300g dark green leafs (with lesser oxalate content)
30-100g nuts and seeds (mostly walnuts, almonds and sunflower seeds, linseeds)
min 500g vegetables in general (without dark green leafs)
fibre: mostly between 50-70g/day, seldon more
oils: mostly olive, linseed and rapeseed also included
25-50g wheat germ/day (because of the vitamine profile and spermidine)

but I did also eat a lot of fruits and berries:
blueberrys 100g/d (european wild berries)
other berries: 100g/d
20g other vacciniae berries
300g of other fruits such as apples, oranges, cataloupes, plums, mangos

I try to reduce it until I see the data for my next blood test. For example: mangos are high in sugar (not fructose)

If I eat grains, it is always whole grain but not wheat (to much sugar).
If I eat bread, it is selfmade from sourdough

main goals per day:

500mg of carotinoides,
50g digestible fibre,
high polyphenole content,
and as much as folate and selenium as I can get from a healthy diet.
None vitamine/mineral should be lesser then 150% RDA.

Also a goal: using diet instead of acarbose - and yes, at least in my case is seems to be possible

It took me a while to figure out which diet is best for me. I started with the diet used from fitzgerald et al. but modified it a lot and also included data from michael lustgarden.
What I can say is: my blood sugre levels (non of them) don’t run rampant on rapa days.

concerning AUC:
yes, you’re right. It is more a good basis for a qualified guessing based on average data. I should also measure Cmax.