“Comparative Bioavailability of a Single Dose of Trametinib (TMT212) Containing 9% vs 11% Dimethyl Sulfoxide in Randomized Healthy Volunteers to Assess Long‐Term Storage at Room Temperature”
This study was sponsored and funded by Novartis Pharmaceuticals Corporation.
FWIW…
A 70-75% solution of DMSO will give you the best absorption through the skin.
.5mg per ml trametinib /DMSO{70-75%] solution, topical on the radial artery on the wrist, closest artery to the skin surface.
Thank you Joseph, that’s an interesting paper that….
These results indicated that storage of trametinib at room temperatures ≤25°C during the overall shelf life of 36 months would not negatively impact trametinib bioavailability.
…opens up the possibility of ordering from India, if the refrigeration requirement for storage/shipping is removed.
Unfortunately, the references cited by Dr. Oracle are behind paywalls. I am only listing two of many citations
Conclusion
Developing a stable liquid formulation of trametinib requires a multifaceted approach. By leveraging ionic liquid technology, optimizing formulation parameters, and employing protective strategies, it may be possible to create a liquid trametinib product that maintains stability without the need for a protective film coating.
Do any of the Indian pharmacies you guys regularly order from carry 0.5mg Trametinib? Anil doesn’t have it.
The pricing I quoted earlier is from Maulik, who can get it for you:
Maulik at Shreeji Impex (ShreejiImpex.com
maulik7@gmail.com
whatsapp: +91 9925171777
website: www.shreejiimpex.co.in
@Shreeji_impex - username for telegram app
If you end up pursuing this, let me know. It would be good to get a standardized set of lab tests / blood tests to do before and afterwards to help identify any side effects of low doses.
I’m talking with Maulik and he confirmed that the Trametinib would be shipped at normal temperature, likely for 10-15 days. It’s a cold storage product, so I’m wondering if this could be an issue, ie either make the med less effective or potentially toxic…
Report from Kamil (a scientist at NSU in Singapore) on ARDD:
In recent years The Aging Research and Drug Discovery Meeting has ascended as one of the most important aging conferences.
All your ERK are belong to us
This ARDD, Linda Partridge presented her work on the combination of trametinib and rapamycin. Trametinib is a MEK inhibitor that leads to reduced MAPK/ERK signalling and synergistic lifespan extension with rapamycin under some circumstances — even in F1 mice that pass the 900-day rule.
Hopefully they will pursue phase I studies soon, because I know for certain that we and others are interested in proper microdosing of trametinib. At the same time the ITP updated their webpage and announces that trametinib is in the ITP (which we knew through the grapevine). Interestingly, even Widaja et al. 2024 showed that pERK phosphorylation is up with aging and that this can be reduced by an anti IL-11 antibody, although I do not fully trust that data because I have rarely seen such strong anabolic upregulation with aging before. Be that as it may, an MAPK/ERK inhibitor is clearly an excellent choice to inhibit ERK!
Unfortunately Maulik informed me today that Trametinib is not available for export…
@RapAdmin are you aware of any other exporters from India that would send the 0.5mg Trametinib?
Summary of the Kaeberlein video: he doesn’t think the tranetinib + Rapamycin study will replicate because the controls didn’t live very long (700-800 days).
His rule of thumb is mouse studies need controls to have around a median 900 day lifespan in order to trust results showing a lifespan extension.
After seeing Kaeberlein’s video I see no reason to jump on the trametinib bandwagon.
To paraphrase Dr. Blagasklonny, “anything” plus rapamycin appears to be better than “anything” alone.
Already in the hopper:
https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/supported-interventions
Yes. When compared to studies with normal-lived controls, the rapa + trametinib male mice did no better than control animals in other studies, and the females did no better than high-dose rapa alone, and substantially worse than strict CR:
I think it’s a good rule of thumb in general but I’ll bet this one replicates. This isn’t a simple test/control, there was a control, trametinib, rapamycin, and the combo. Not only did trametinib and rapamycin outperform the (short-lived) controls, but the combo outperformed rapamycin and trametinib alone. It’s not just a one-off result, it’s a trend. If you don’t believe the control group is valid, you can drop them and still come to the conclusion that the addition of trametinib improves lifespan over rapamycin alone.
Pricing in Mexico is now below US $1500 per 30 x 0.5mg Trametinib (Resultado de tu búsqueda: 1 resultado relacionados a "Mekinist 0.5mg" – Farmacia Santa Rita), so under $50 per tablet. Due to the high cost most smaller pharmacies won’t carry it but larger pharmacies will deliver to any smaller pharmacy in Mexico for pickup, so those living on the US border to Mexico might be able to get it for a reasonable price, without worrying about refrigeration or customs impoundment. Since the dosage would be 0.5mg every 20 days, that is around $2.5/day.
This line of mouse is bred for sensitivity to carcinogens and trametinib is a kinase inhibitor. How much of the longevity outcome is accounted for along those lines of effect?
This research group saw the same benefits from the combination of drugs in their earlier studies with drosophila, so that doesn’t seem very relevant.
Probably not and I get it but the drop off of relevance between flies, mice, and men is a really steep curve. As of today, there is no randomized controlled research demonstrating that rapamycin causes a longer life, or much of anything passing a risk/benefit analysis.
There are five experimental trials underway with the following endpoints and stages:
The paper finally published (the first post in this thread was the pre-print version).
Open access Paper:
Suppression of the insulin–IGF–mTORC1–Ras network ameliorates aging in animals. Many drugs have targets in the network because of its roles in cancer and metabolic disease and are candidates for repurposing as geroprotectors. Rapamycin, an established geroprotective drug, blocks mTORC1 signaling, and trametinib inhibits the Ras–MEK–ERK pathway. In this study, we assessed survival and health of male and female mice treated with trametinib, rapamycin or their combination. We show here that trametinib treatment extended lifespan in both sexes and that its combination with rapamycin was additive. Combination treatment reduced liver tumors in both sexes and spleen tumors in male mice, blocked the age-related increase in brain glucose uptake and strongly reduced inflammation in brain, kidney, spleen and muscle and circulating levels of pro-inflammatory cytokines. We conclude that trametinib is a geroprotector in mice and that its combination with rapamycin is more effective than either drug alone, making the combination a candidate for repurposing as a gerotherapy in humans.
