His rapamycin blood level down from 20.4 ng/ml to 2.9 in 24 hours, much less than expected 63 hours…
Maybe healthy adults can metabolize rapamycin much faster than organ transplant patients, which is the half life of rapamycin based on?
Anyone has measured rapamycin blood level, before taking it and every 8 hours after taking it?
Very important observation. Especially since almost all the rapa-science made on mice, use mice that are continously fed. And therefore living with a rather constant inhibition of mTOR.
I already watched this, and I always enjoy Matt’s perspective. He is in pretty good condition, and I would not expect the average middle aged Rapamycin user to clear the medication this quickly, but that is just a guess.
Also, Bryan took his Rapamycin with olive oil that we know flattens the peak, and Matt did not specify how he administered his dosage. Still worthwhile data, though.
Do we know how half life was determined?
So, I’m a little bothered by this. Matt K is a scientist. He does a study, albeit n of 1, and gets results that are dramatically unexpected. A half life 8 fold different. But he doesn’t repeat the study?
I’ve commented on this one before. Sadly this is an error on his part. He checked a level very early on which represents absorption but not tissue redistribution. So the peak level he got early isn’t what he should be using, if he checks a level at 12 hrs then at 24 hrs for example he will have more appropriate data. I usually get patients to a 5.5 blood level or so at 20 hrs then recheck 48 hrs later … most are in a range of half life mid 30s to mid 40s in hrs, not 8 hours. The pharmalogical data on this drug is correct as published.
This for example is part of the reason an acetaminophen monogram for toxicity starts at 4 hrs, it is only then that we really can predict with confidence whether we have a toxic ingestion. The levels are crazy high at 1 hr but we need to see where they settle to at 4 hrs to understand the continuing metabolism and risk. The very early levels aren’t reliable enough as they represent multiple factors, just like in this case.
No idea, i guess it must be from pharmaceutical company. Consider the efficacy of taking rapamycin to delay aging, a shorter half life means we can take it more often without suppressing mTOR C2.
May i say 30-40 hours of half life are also rather quick compared to the well known standard 63 hours.
His results are not that unexpected. He does not have a kidney transplant. Also, I would not call it a study, it was his personal experience. He has shared this kind of data before. Not sure why this would bother you.
Your method may get useful data, but that is not how half life is measured.
It’s a big impact on how often we can take rapamycin without side effects, if Matt’s data is correct. It’s natural we hope he can be very sure.
Probably our weekly dose are too modest to really have an efficacy on delaying aging?
No this is all consistent. Single doses of rapa average around 35 hrs … daily dosing is in the 60s. As we get bigger single doses they start metabolizing a bit more daily dosing.
The comment on Dr not being a kidney transplant patient isn’t relevant, this is not renal metabolized, it is primarily hepatic metabolism.
You can absolutely see 2 serial levels and note the interval between those and estimate half life. There are drugs that have zero order metabolism where that isn’t the method, but that was certainly the teaching when I did my graduate pharmacology courses. I’m happy to learn if you are a specialist in drug metabolism and have a critique.
@Stijn do you have a color to offer as an expert at testing rapa blood levels
For others, see context here:
Matt Kaeberlein didn’t say whether or not he exercised during that period.
Since rapamycin and exercise are at odds with each other, would exercising the next day shorten the half-life of rapaycin?
We also don’t know what supplements he was taking the day of rapamycin or the day after.
"Creatine Supplementation: Creatine supplementation has been found to amplify the resistance exercise-induced decrease in serum myostatin, potentially by activating mTORC1 and increasing insulin-like growth factor-I (IGF-I) activity at rest’
"Resistance exercise can potentially affect medication half-life through the following mechanisms:
Increased Blood Flow and Metabolism
During resistance exercise, there is an increase in blood flow to the muscles and other tissues. This increased blood flow can potentially enhance the delivery of the medication to its target sites, leading to faster absorption and distribution. Additionally, the increased metabolic rate during exercise may accelerate the metabolism and elimination of certain drugs, potentially shortening their half-life.
Changes in Protein Binding
Exercise can cause changes in plasma protein levels, which may affect the binding of drugs to these proteins. If a drug is highly bound to plasma proteins, changes in protein levels could alter its distribution and elimination, potentially affecting its half-life."
In the study below, “Healthy volunteers were administered a 15 mg single dose of sirolimus on two occasions, once while fasting and once after consumption of a high-fat breakfast.”
Despite the fact that the breakfast increased absorption by 35%, there was no difference in the terminal half-life, which was an average of 67 to 68 hours.
The point isn’t to sort out why his half life is 8 hrs. The point is he has made a fundamental error and his half life isn’t 8 hrs.
So one of my pts takes 9 mg w GFJ and at 20 hrs has a level of 7.2. I get a level 48 hrs later and it is 3.4. So if it were 3.6 then his half life would be 48 hr as half of the drug would be gone. In his situation slightly more than half was metabolized… so it would be roughly 43 hrs give or take.
So if I’m concerned about time someone is over 3.0 I would know that he will be north of this for at least 85 hrs give or take … with that dose.
So then for dosing interval … I’m going to want it about 3 times that 85 hrs.
I’m not formally doing the math, but these are close.
It’s important to note a lot can be done in absorption and if taking GFJ seems more on absorption than rate of metabolism at least on just taking 2 doses of GFJ 12 hrs apart.
But exercising and most other things will make very little difference.
The half life was established in kidney transplant patients from what I have read. These patients are obviously not in the best health, take other medications, and I believe it is common for them to have hepatic impairment. Half life, as you know, has many variabilities from patient to patient.
Sure, the half life can be extrapolated as you say and in some ways be more useful. However, Matt Kaeberlein’s method was pretty close to what the AMA and NIH recommend.