Levothyroxine Tablet Malabsorption Associated with Gastroparesis Corrected with Gelatin Capsule Formulation

[Portia1974]

Wondering if anyone has any thoughts or experience relating to poor absorption of Levo. I'm convinced I have gastroparesis and am pushing my GP for a referall for a gastric emptying study to check for this. Just wondering how common this is:

ncbi.nlm.nih.gov/pmc/articl...

[Hibs1]

I have slow digestive system due to undiagnosed Coeliac disease all my life till two years ago. Leaving me with chronic constipation. I am in prescription laxatives from gastro clinic so I wonder about the absorption of levo with the sodium too

[Portia1974 in reply to Hibs1]

I feel like it has to affect it.

[helvella Administrator]

I am quite convinced that some people do not absorb well for a variety of reasons.

That paper, though, does not explain why gelatin capsule levothyroxine works better than tablets. I struggled to come up with any possible explanation.

[Portia1974 in reply to helvella]

I'd guess because the shell dissolves quicker than a hard tablet and the contents are liquid which also absorbs better? I can imagine in a low acid environment it's plausible a tablet could pass through barely touched.

[helvella Administrator in reply to Portia1974]

Time doesn't seem to be a prime issue as gastroparesis means that there should be lots of time in the stomach!

If the stomach doesn't empty, then it will be far more likely that any medicine will enter a stomach which either already has, or will later have, food in it. If levothyroxine is affected by food, a faster dissolving gelatin capsule would appear, if anything, to allow a longer time for the levothyroxine to react with that food.

Primary absorption of levothyroxine is further down in the intestine - the duodenum, jejunum and ileum.

The paper doesn't say anything about the tablets - such as the make - some disperse almost instantly upon contact with moisture (Levoxyl being the prime example).

I agree it is in interesting paper, and its message should be picked up by doctors. But how I wish for a proper explanation.

[Portia1974 in reply to helvella]

The plot thickens lol!

[Portia1974 in reply to helvella]

Just out of interest, is T3 absorbed in the same part of the digestive tract do you know?

[Portia1974 in reply to helvella]

Also...reading the paper again they do appear to hypothesise that something in the tablet form binds to food but whatever is in the capsule formulation does not. Interesting.

"Food and even beverages such as coffee have been shown to retain levothyroxine sodium tablets in the intestinal lumen resulting in a decreased bioavailability [10]. This is likely the reason for the lack of response observed in this patient as subsequent meals may have sequestered appropriately administered doses and decreased absorption."

(Which is exactly what you said)

"The gelatin capsule formulation, unlike the tablet formulation, is unaffected by concurrent consumption of coffee [11]. The gelatin capsules may be able to bypass the sequestering mechanism of traditional levothyroxine preparations resulting in better absorption and treatment efficacy in patients with gastric and intestinal malabsorption issues [7]"

It also specifies a particular formulation:

"Tirosint® (Akrimax Pharmaceuticals, LLC, Cranford, NJ, USA) is a levothyroxine sodium gelatin capsule that contains T4 dissolved in glycerin. This formulation has been shown to have the most consistent dissolution pattern which results in a more reliable bioavailability. In patients with impaired gastric acid secretion, the gelatin capsule formulation was shown to maintain similar median TSH levels despite a 17% lower dose of levothyroxine compared to a tablet formulation [4]."

[helvella Administrator in reply to Portia1974]

Many of the reports regarding Tirosint were done by people with some sort of relation to the manufacturer.

Whilst this does not mean they are untrue, a pinch of salt does seem sensible.

What is often missed is that levothyroxine is remarkable insoluble - in neutral or acidic solutions. It is more soluble in alkaline solutions.

The stomach is acidic.

This gets rapidly neutralised and alkalinised almost immediately the stomach empties.

Perhaps simply being at least semi-dissolved is the key?

I don't know - but we might have hoped that in the 60+ years since levothyroxine was synthesised and available, someone would have done some serious and detailed research into absorption. (Or maybe not. )