Thanks @Agetron - I’m glad you let me know this - I will be having a chat this week. A bit humbling to speak with a legend.
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Exactly, Matt K. Is one of the few knowledgable researchers without an agenda… except… wanting to explain what does the evidence point to… and is the work accurate using proper scientific methods. Very methodical and trusted.
And, geeky, funny and humble too.
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AmyK
#55
That’s very helpful. Thank you.
I’m having serolimus blood tests done at 2, 4 and 6 hours after I take 8mg simply to determine IF the seroboon 2mg tablets I bought from India actually have any serolimus in them.
For my test last Monday I cut up four, 2mg tablets so I could stuff them into two acid resistant capsules as I read it might be a good idea to get them through the stomach and into the small intestine for better absorbing. There was no detectable serolimus in my blood at the intervals tested.
Next Monday I will repeat the test but will take the four pills in naked form.
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Bless your heart… taking all those pokes in the vein.
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2nd experiment 7 days after the 1st wherein Sirolimus blood levels were non detectable.
3 blood draws, 2 hours apart beginning 2 hours after taking 4 Siroboon, 2mg tablets= Sirolimus of 2.1 to 1.1 ng/ml.
From this and my draws of one week prior I think it’s safe to conclude that Siroboon has nearly zero Sirolimus in it…I wasted $260 buying 300, 2mg tablets from India. I feel fortunate that taking Siroboon weekly for several months has evidently caused me no harm.
Next step: get an Rx from my local Dr, buy Rapamycin from a local pharmacy and repeat the experiment as soon as I receive my new Rx.
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George
#59
I suppose the company which originally launched rapamycin would have done a Phase I study in healthy adults which would also include half-lives… Not sure where you can find the data if they did not publish it. If you look at the Drug Master Files of the original application, it would show the data
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Maxi
#60
Yes, I measured my peak and half life (see post “Peak Values and Half Life”, unfortunately the graphs didnt come out) and found in multiple measurements a half life of 6-8 hrs, which is plausîble as I am, according to my pharmacogenetic profile, a rapid metabolizer of 3A4. So I have a good peak but AUC is too low ! I want to increase my half life, many 3A4 inhibitors available but problematic or difficult to dose. So i’ll try with GPJ by taking it 2.5 hrs after Rapa, which is where my peak lies. Any comments/suggestions on AUC improvement w/o increasing peak ?
The simple solution is just to split your dose into two days; take half of the dose on one day and the other half the next day. Then your AUC will approximate that of someone with average half-life that takes all the dose at once .
Maxi
#62
Thank you, that would probably increase AUC by creating a “double peak”, but the peaks would be lower than with the single dose. At 14 mg my avg peak is 66 ug/l. I believe a high peak is necessary to antagonize mTOR1 enough to increase autophagy ?
I don’t think a high peak is important at all. Transplant patients maintain fairly stable moderate levels by dosing every day, yet they get plenty of mTORC1 inhibition by doing so.
The grapefruit juice doesn’t act to slow the metabolism. Instead it acts in the intestinal wall to inhibit CYP3A4, which then blocks the intestinal breakdown of the Rapamycin and allows, on average 3 times more to be absorbed across the bowel.
To my knowledge, once the drug is in your blood stream, GFJ does not change your metabolic half life.
So the typical timing if wanting more to be absorbed is a few hours before taking rapamycin - take the GFJ usually 8 oz, then I take 4 oz at the time of taking it also. This, in my case allows me to take 1/3rd the dose I’d need to achieve the levels compared to without GFJ.
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Beth
#65
How long after the dose can you take grapefruit (or in my case pomegranate juice/fruit) without effecting the levels?
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59vw
#66
@Beth the best answer to your question would be to do an experiment and check and see. For example take your weekly dose, wait 0, 1, 2, 3, hours take GFJ and measure blood levels at 48 hours (of course on 4 different weeks.
However we know that peak levels occur within 2-3 hours of ingesting sirolimus in the pill form so likely grape fruit juice will have minimal to no affect after about 3 hours. Likely even earlier because 90% of the absorption has already occurred.
If on the other hand you are just wondering if you can drink GFJ the next day well then I think that would be unlikely to have any affect on your blood levels of sirolimus.
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Beth
#67
@59vw,
I was told to have daily pomegranate (fruit/juice/powder/etc) but not to have it 36 hours prior to my rapa dose. I had no idea how long afterwards I needed to wait before starting it again, so I really appreciate your input.
It sounds like I can definitely have it the following day, and perhaps even at the end of the same day if I take my rapa in the morning.
It happens to be the following day, so now I’ll go eat my pomegranate! THX AGAIN!
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That’s amazing. I always assumed it worked in the liver. Thanks for sharing the info.
While we’re here in this resurrected old thread, if a person wanted to test their Rapa levels and calculate their own T1/2, what blood timings would you recommend after they’ve taken their regular dose?
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Maxi
#69
cl-user
#70
Yes, but the inhibition also in the liver is much less compared to the inhibition in the gut so you need to take high doses of GFJ for the inhibition in the liver.
Here they used double strength GFJ for 3 days do see some inhibition in the liver (doubling of the half-life) but a single glass of single or double strength GFJ did not change the half-life.
It was concluded that consumption of one glass of DS GFJ tid for 3 days significantly increased the AUC, Cmax, and t1/2 of midazolam and reduced EBT values, reflecting inhibition of both hepatic and intestinal CYP3A4. In contrast, consumption of one glass of SS or DS GFJ increased midazolam AUC and Cmax, with little effect on the midazolam t1/2 and EBT values,
cl-user
#71
Generally 48h and 96h. You need to get past the intake peak and be in the equilibrium phase.
If you want the full pharmacokinetics profile you need 4 points as explained in those threads:
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Hmm … not really. [click to see some data on this]
Not at typical amounts.
The nice thing with doing a 50 hr level if dosing weekly or 100 hr level if dosing every 2 weeks is that it controls for all of this, so long as you do everything the same each time.
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