Thyroid hormone (levothyroxine) replacement via the respiratory route by inhalation

There seems to be one phrase buzzing around my head as I read this: Suck it and see. :-)

Not a lollipop but an interesting idea. After all, many here are deeply suspicious about the effect of thyroid hormone medications on the gut.

Expert Opin Drug Deliv. 2015 Dec 18:1-11. [Epub ahead of print]

Thyroid hormone (levothyroxine) replacement via the respiratory route by inhalation: in vitro exploratory studies.

Agu RU1, Mactavish J1, Yeung PK1, Imran SA2.

Author information

1a College of Pharmacy , Dalhousie University , Halifax , Canada.

2b Division of Endocrinology & Metabolism, Faculty of Medicine , Dalhousie University , Halifax , Canada.



To conduct proof of principle studies that will enable development of noninvasive (respiratory) delivery systems for levothyroxine (T4).


Preformulation (solubility, stability), formulation and biopharmaceutical (in vitro absorption, transport, gene expression) studies were conducted. Calu-3 cell line was used for permeation studies.


Solubility profiles of T4 were established in aqueous (PBS, HBSS, isotonic saline) and non-aqueous solvents (PEG 400, PEG 600, propylene glycol, glycerine). Transport of the compound across Calu-3 cells suggested involvement of active transport systems. This correlated with expression of thyroxine transporters (MCT8, MCT10, OATP1A2, LAT1 and LAT2) in the cell line. Diffusion characteristics showed significant absorption with no detection of T4 metabolite (triiodothyronine). Formulation studies revealed that stable formulations could be prepared using a combination of aqueous and non-aqueous solvents.


Results of the studies indicated that T4 can be absorbed effectively from the respiratory mucosa. Factors affecting stability such as pH and temperature should be taken into account during formulation development of this compound for the respiratory route.


Calu-3; levothyroxine; respiratory delivery; thyroid hormone transporters; thyroid hormones

PMID: 26684066 [PubMed - as supplied by publisher]

Full text not accessible.

9 Replies

  • This would be marvellous. No worries about unwanted binding proteins and gut absorption issues.

    What about a T3 equivalent Helvella?


  • Certainly seems sensible to try liothyronine as well.

    But I can't see a desiccated porcine inhalation happening!

    I thought it interesting that the non-aqueous solvents they mention (PEG) are more-or-less what is used in vaping...

  • The pig option might be a bit smelly anyway !



  • Helvella, Should be very useful for those with malabsorption issues if the spray can deliver accurate doses.

  • The paper wasn't clear (to me) about whether the delivery was expected to be for a few seconds/minutes one or more times a day. Or for hours - such as might happen with someone on an oxygen delivery system. Quite possibly they don't yet know themselves.

  • Helvella, Can't imagine delivery over hours on oxygen will be very helpful but one or more doses via a nasal spray or asthma type inhaler seems feasible.

  • In the very sad case of body being kept alive for transplant purposes, it might be very appropriate to deliver continuously with air/oxygen. And there are now quite a lot of papers which claim that dosing with T4, T3 or a combo help with retrieving usable organs.

  • Helvella, I didn't know dosing T4 & T3 helped preserve organs for transplant. Roll on the day it becomes widely available to enable patients to live well.

  • There are many papers on both sides of the fence (that it helps or that it doesn't). One pro paper:

    It sometimes appears that with transplant teams, psychiatrists, heart surgeons and others using thyroid hormones including T3, the ones who don't/won't are the endocrinologists.

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