Liquid T4 and central hypothyroidism

[diogenes]

An abstract from the ATA symposium showing superior preformance by liquid T4 for those with central hypothyroidism.

L-THYROXINE IN AN ORAL LIQUID OR SOFTGEL FORMULATION ENSURES MORE NORMAL SERUM LEVELS OF FREE T4 IN PATIENTS WITH CENTRAL HYPOTHYROIDISM S. Benvenga, G. Capodicasa, S. Perelli. 1University of Messina, Messina, Italy; 2University hospital AOU Policlinico G. Martino, Messina, Italy

L-thyroxine therapy of central hypothyroidism (CH) is guided by measurements of serum free T4 (FT4), which should be above the midnormal range value (MNRV). In some countries, novel formulations of oral L-thyroxine (liquid or softgel) are available further to the classic tablets. The intestinal absorption of either novel formulation is greater than tablets in patients with primary hypothyroidism. Our observation of six patients with isolated CH and serum FT4 below MNRV under stable adequate doses of tablet L-thyroxine (median 1.51 lg/Kg/day bw), prompted us to switch them to liquid (n=4) or softgel (n=3) L-thyroxine at the same dose, and verify whether FT4 increased above MNRV. A seventh patient with FT4 above MNRV was enrolled because she wanted a ‘‘more modern formulation’’. Post-switch FT4 was measured at least twice with the same kit as pre-switch FT4. In the first six patients, post-switch FT4 averaged 13.0–1.6pg/ml compared to 10.4–1.8 pre-switch FT4 (P = 0.00026), with 11/13 (85%) measurements above MNRV compared to 0/20. In the liquid or softgel L-thyroxine group, post- switch FT4 averaged 13.1 – 1.6 vs 10.6 – 0.9 pg/ml pre-switch (P=0.0004) or 12.9–2.1 vs 10.3–2.4 (P=0.048). In the seventh patient (switched to liquid L-thyroxine), averages were 18.3 vs 15.2 pg/ml and proportions 4/4 vs 2/2. In conclusion, in CH patients oral liquid or softgel L-thyroxine administered at the same doses as tablet L-thyroxine ensures target serum FT4 levels above MNRV that tablet L-thyroxine may miss. In turn, this performance confirms the more favorable pharmacokinetics profile of either novel formulation compared with the tablet formulation.

[amala57]

When if ever will we get this in the dark ages of the uk?

[helvella in reply to amala57]

Liquid formulations are available.

Gel cap formulations do appear to be getting wider availability across Europe - but not, yet, the UK.

Main issue for many is the much greater cost - translating into unwillingness to prescribe.

I have seen many papers claiming advantages to gel caps - and cannot remember a single negative. (Except for the non-vegetarian nature of them.) Liquid formulations typically supply a hefty dose of glycerol which is not always tolerable.

[helvella]

Marz

I noticed this Greek link:

translate.google.co.uk/tran...

In my ignorance, it looks as if IBSA's gel caps might be available in Greece. Do you know anything of this?

[Marz in reply to helvella]

Will check. In UK at the moment !

[ITYFIALMCTT]

Different formulations of conventional drugs do look as if they can have substantial advantages. E.g., I don't tolerate even standard doses of NSAIDs at all well so was interested to read a pre-print of this paper on a lipid NSAID. It looks like this formulation has the same effect as double the oral dosage - so, for somebody like me, it might be possible to minimise the amount that I need to take and possibly bring it within tolerable side-effects.

I've no idea what the cost of this will be or if it will just be OTC - tho' given the amount the NHS is spending on PPIs and other ways to handle the side-effects of NSAIDs, it would have to be ludicrously costly not to be cheaper than the add-on costs for some groups of people.

Bierma-Zeinstra SMA, Brew J, Stoner K, Wilson R, Kilbourn A, Conaghan PG. A new lipid formulation of low dose ibuprofen shows non-inferiority to high dose standard ibuprofen: the FLARE study (flaring arthralgia relief evaluation in episodic flaring knee pain) - a randomised double-blind study.. Osteoarthritis Cartilage. 2017;

[jimh111]

Only seen the abstract but this seems a confusing study. Not sure why they tried it in central hypothyroidism patients, whether they have any specific needs, given a trial has already been carried out in primary hypothyroidism patients. The study shows that liquid levothyroxine is better absorbed than tablets, which is no surprise. I would have thought they could have achieved the same target fT4 levels by simply increasinig the tablet dose a little.

Liquid levothyroxine is vastly more expensive than tablets, so it makes sense for most patients to be on tablets. However, patients who have problems breaking down the tablets due to concurrent drugs or gastric problems absorb liquid levothyroxine much better and so it makes senese to give it to these patients.

I really wonder why they can't just make tablets that are easily absorbed, surely a tablet is just a dry liquid? (Assuming the liquid is water based).

[helvella in reply to jimh111]

Interesting then that there is a liquid liothyronine available in Italy which is based on ethyl alcohol and some glycerol. Perhaps we shouldn't assume that liquid is water-based?

Called Liotir.

[diogenes Remembering in reply to helvella]

T4 and T3 aren't very water soluble.

[jimh111 in reply to diogenes]

True, I was being a little flippant as well as some later thinking. I'm sure the late Dr Skinner would have recommended a glass of Scotch to aid absorption! Nonetheless the pharmaceutical companies should be able to come up with a tablet or softgel which is both cheap and has good consistent absorption. Liothyronine on the other hand has 95% absorption.

[helvella in reply to jimh111]

Flippancy aside... Unfortunately, levothyroxine is Insoluble in ethanol, benzene - so Scotch is unlikely to be of much help.

pubchem.ncbi.nlm.nih.gov/co...

[jimh111 in reply to helvella]

Now I'm really confused, because ethyl alcohol is ethanol! Anyway , the liquid form is better absorbed, that's a fact.

[helvella in reply to jimh111]

The Italian product is referred to is Liothyronine. - Yes - well aware that ethanol = ethyl alcohol. I only switched because I was quoting.

[diogenes Remembering]

As I see it, tablet formulation is subject to all kinds of potential interference. 1) Time for gastric acid pH to dissolve it before entering lower intestine. 2) Interplay between food substances, gastric pH and uptake, 3) lower down food and food derivatives interference with uptake, 3) overall intestinal absorption ability given all the above potential interference, before the bolus has passed irretrievably down to the large intestine. Perhaps gel or liquid allows better gastric uptake high up before the complications lower down interfere.