This is a hot preprint which describes the use of an analogue of T3 that stabilises T3 levels in the body. It is a very visible sign that US medics are taking T3 therapy seriously.
EXTENDED ABSORPTION OF LIOTHYRONINE FROM POLY-ZINC LIOTHYRONINE (PZL) IN HUMANS
June 2021
DOI: 10.1101/2021.06.14.21258437
Alexandra M. Dumitrescu, Erin C Hanlon, Marilyn Arosema, AntonioBianco A et al
Background: Liothyronine (LT3) has been increasingly used in combination with levothyroxine (LT4) in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical T3 peak seen after oral administration of LT3. Objectives: To evaluate in healthy volunteers (i) the pharmacokinetics of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) monitoring for the adverse events; (iv) exploratory analysis of the sleep patterns after LT3, PZL or placebo administration. Methods: 12 healthy volunteers 18 to 50 years of age were recruited for a Phase 1, double-blind, randomized, single-dose placebo-controlled, cross-over study to compare PZL against LT3 or placebo. Subjects were admitted three separate times to receive a randomly assigned capsule containing placebo, 50-mcg LT3, or 50-mcg-PZL, and were observed for 48h. A 2-week wash-out period separated each admission. Results: LT3-derived serum T3 levels exhibited the expected profile, with a Tmax at 2h and return to basal levels by 24-36h. PZL-derived serum T3 levels exhibited a ~30% lower Cmax that was 1 h delayed and extended into a plateau that lasted up to 6h. This was followed by a lower but much longer plateau; by 24 hours serum T3 levels still exceeded 1/2 of Cmax. TSH levels were similarly reduced indistinguishably in both groups. Conclusion: PZL possesses the necessary properties to achieve a much improved T3 pharma-cokinetic. Drug product development of PZL should improve the delivery of T3 even further. PZL is on track to provide hypothyroid patients with stable levels of serum T3.
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diogenes
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Thanks, will read later. This is good news, it may be no better than current L-T3 in practice but it undermines the irrational objection to the pharmacokinetics of L-T3 (T3 takes a lot longer to get into cells and effect transcription than the short time in the blood). Good also that they look at sleep patterns, this is a great way of observing T3 effects in the brain.
Do we know anything of the processes involved in making PZL?
Obviously, cost to pharmacies and health services is very much a commercial decision. But it would be nice to have at least an inkling as to whether it is likely to have a low, medium or high cost of production.
The UK will as usual go through a long drawn out enquiry into the analogue's safety and efficacy - not taking the US FDA's decision as read, but reinventing the wheel. Remember the dread words the UK gurus use - insufficient evidence. According to whom? Why according to them only.
Gulp that’s a bit complex especially for someone with zero chemistry knowledge…unfathomable in fact. It’s sure to cost a small fortune here… it doesn’t look simple to me.
Patents are somewhat difficult to read - especially with all their bits that try to say "and anything even slightly like this" so as to extend the scope of the patent while not getting it struck out for being too much of a blanket application!
However, I thought it might be of interest in that there is some brief description of what the final substance is and an outline of how to make it.
But what about the battle with the endocrinologists after that? It’s another 30- 40 years before the old intransigent flange die off and fresh minds move in, assuming they haven’t been brainwashed, and can eventually effect change.
Exactly. I just look after myself the best I can. As long as I can get hold of ndt, I should be OK. I feel totally abandoned by the NHS where my thyroid is concerned. 😔
My sentiments exactly I do worry about where I will get NDT from in the future it’s pretty rubbish they can shut down our suppliers fast as you know but can’t seem to do anything about choking off child porn - it’s disgusting.
Study shows that both L-T3 and PZL have the same effect on TSH. This is a question that has hung around, does the short term peak in fT3 (or tT3) have an excessive effect on supressing TSH. It seems it doesn't, that TSH responds to overall T3 levels i.e. the area under the curve. It also gives a bit more confirmation that cellular response to T3 occurs over a period of hours, i.e. short term fluctuations in T3 don't matter, don't cause harm as some endocrinologists have speculated.
That's right! Rises in FT3 need a finite time for the stimulation of that to show itself. In the meantime, FT3 levels then fall rather quickly so that the overall response now is lower. That is, the spike in FT3 is damped off in its actions so that the actual biochemical response changes over time are much less affected, Or, plotting FT3 rises and falls would show a much less obvious response biochemically. Let me put it this way: I don't think an T3-analogue is going to change much, only a smaller hump in FT3 values to satisfy those who think the FT3 spike is dangerous.
If the Americans/ developers have any sense they will price it just below the current of price of T3 and incentivise endocrinologists to switch people over. As the only cheaper option they will have several years without competition to let the money roll in.
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