A novel levothyroxine solution results in similar bioavailability whether taken 30 or just 15 minutes before a high-fat high-calorie meal
Open accessAbstract
Background: Levothyroxine (LT4) sodium is a standard treatment for hypothyroidism. Its absorption and bioavailability when taken as a tablet have been shown to be significantly decreased with concomitant food ingestion. Therefore, LT4 formulations are recommended to be taken on an empty stomach, at least 30, ideally 60, minutes before breakfast, potentially affecting adherence to therapy. A novel LT4 solution (Tirosint ® -SOL) has been shown to result in a faster absorption process than tablets or soft-gel capsule formulations. The objective of this trial was to evaluate the bioavailability of this preparation taken 15 minutes before a high-fat high-calorie meal in comparison with the minimally recommended 30-minute interval. Methods: Thirty-six (33 completers, 24 males and 9 females) healthy volunteers participating in the randomized study took 600 mcg of LT4 oral solution, single doses after a 10-hour fast, 15 or 30 minutes before a high-fat, high-calorie, FDA-approved standardized meal in a controlled research setting. We measured serum total thyroxine using Liquid Chromatography with Tandem Mass Spectrometry at baseline and multiple time points up to 72 hours after LT4 administration. The predefined equivalence boundaries for the extent of exposure reflected by the area under the curve (AUC) were 80–125%. The washout period was at least 35 days. Results: The geometric mean ratios and confidence intervals (CIs) for the baseline-adjusted extent of exposure represented by AUCs truncated at both 48 and 72 hours after dosing (AUC 0–48 : 90% [90% CI 86–94]; and AUC 0–72 : 92% [90% CI 87–97]) were within the prespecified equivalence boundaries. The baseline-adjusted peak concentration was also clinically similar (C max : 85% [90% CI 80–90]). The median t max was 1.5 hours in each group. The rate of adverse events was similar between groups. Conclusions: We observed no significant difference in the pharmacokinetic properties of a novel LT4 solution administered 15 and 30 minutes before a high-fat high-calorie meal in normal subjects. Further research is needed to evaluate (a) the differences in overall bioavailability at other time points (including immediately premeal) and (b) the real-world effectiveness of this preparation in newly proposed administration conditions to optimize treatment outcomes in hypothyroid patients.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Taken together, the convenience of the liquid preparation improves patient compliance.
“Taken together, these data show that the convenience of the liquid preparation improves patient compliance.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [210]
A randomized crossover trial demonstrated that food interference could be eliminated by liquid LT4 when taken 15 minutes before high-fat, high-calorie meals.
“Surprisingly, a randomized crossover trial conducted by Ducharme et al has demonstrated that food interference could be eliminated by liquid LT4 when taken 15 minutes before high-fat, high-calorie meals (210).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [210]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
Self-citationChaker, L., Bianco, A. C., Jonklaas, J., & Peeters, R. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30703-1 · Cited by 1,159 · see citing works
Growing pains: Non‐adherence with the immunosuppressive regimen in adolescent transplant recipients
Dobbels, F., Damme‐Lombaerts, R. V., Vanhaecke, J., & Geest, S. D. (2005) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2005.00356.x · Cited by 379 · see citing works
Timing of levothyroxine administration affects serum thyrotropin concentration
Bach-Huynh, T.-G., Nayak, B., Loh, J., Soldin, S., & Jonklaas, J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0860 · Cited by 198 · see citing works
Ehrenkranz, J., Bach, P. R., Snow, G. L., Schneider, A., Lee, J. L., Ilstrup, S., Bennett, S. T., & Benvenga, S. (2015) · Thyroid · doi:10.1089/thy.2014.0589 · Cited by 190 · see citing works
A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism
Colucci, P., Yue, C. S., Ducharme, M., Benvenga, S., Principal Scientist, L. A. C. I., Principal Scientist, L. A. C. I. A. P. C., President and CEO, L. A. C. I., & Professor of Medicine, D. (2010) · European Endocrinology · doi:10.17925/ee.2013.09.01.40 · Cited by 167 · see citing works
Self-citationAspects of the absorption of oral L-thyroxine in normal man
Wenzel, K. W., & Kirschsieper, H. E. (1977) · Metabolism · doi:10.1016/0026-0495(77)90121-4 · Cited by 151 · see citing works
Lillevang-Johansen, M., Abrahamsen, B., Jørgensen, H. L., Brix, T. H., & Hegedüs, L. (2018) · Thyroid · doi:10.1089/thy.2017.0517 · Cited by 150 · see citing works
Thayakaran, R., Adderley, N. J., Sainsbury, C., Torlinska, B., Boelaert, K., Šumilo, D., Price, M., Thomas, G. N., Toulis, K. A., & Nirantharakumar, K. (2019) · BMJ · doi:10.1136/bmj.l4892 · Cited by 138 · see citing works
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Skelin, M., Lucijanić, T., Amidžić Klarić, D., Rešić, A., Bakula, M., Liberati-Čizmek, A.-M., Gharib, H., & Rahelić, D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.005 · Cited by 133 · see citing works
Effects of Evening vs Morning Levothyroxine Intake: A Randomized Double-blind Crossover Trial
Bolk, N. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.436 · Cited by 128 · see citing works
Vita, R., Saraceno, G., Trimarchi, F., & Benvenga, S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2684 · Cited by 99 · see citing works
Treatment of Hypothyroidism with Once Weekly Thyroxine1
Grebe, S. K. G., Cooke, R. R., Ford, H. C., Fagerström, J. N., Cordwell, D. P., Lever, N. A., Purdie, G., & Feek, C. M. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.3.3830 · Cited by 95 · see citing works
Levothyroxine interactions with food and dietary supplements – a systematic review
Wiesner, A., Gajewska, D., & Paśko, P. (2021) · Pharmaceuticals · doi:10.3390/ph14030206 · Cited by 85 · cited 1× · see citing works
“Recent studies have suggested that the effect of food on LT4 could be minimized by replacing tablets with an oral solution (32).”
BackgroundYue, C., Scarsi, C., & Ducharme, M. P. (2012) · Arzneimittelforschung · doi:10.1055/s-0032-1329951 · Cited by 81 · see citing works
Self-citationCappelli, C., Pirola, I., Daffini, L., Formenti, A., Iacobello, C., Cristiano, A., Gandossi, E., Agabiti Rosei, E., & Castellano, M. (2016) · Thyroid · doi:10.1089/thy.2015.0422 · Cited by 80 · see citing works
Treatment of Hypothyroidism with Once Weekly Thyroxine
Grebe, S. K. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.3.870 · Cited by 68 · see citing works
McMillan, M., Rotenberg, K. S., Vora, K., Sterman, A. B., Thevathasan, L., Ryan, M. F., Mehra, M., & Sandulli, W. (2016) · Drugs in R&D · doi:10.1007/s40268-015-0116-6 · Cited by 64 · see citing works
Serum Thyrotropin Levels Following Levothyroxine Administration at Breakfast
Perez, C. L. S., Araki, F. S., Graf, H., & de Carvalho, G. A. (2013) · Thyroid · doi:10.1089/thy.2012.0435 · Cited by 63 · see citing works
Virili, C., Giovanella, L., Fallahi, P., Antonelli, A., Santaguida, M. G., Centanni, M., & Trimboli, P. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00010 · Cited by 61 · see citing works
Viswanathan, M., Golin, C. E., Jones, C. D., Ashok, M., Blalock, S. J., Wines, R., Coker‐Schwimmer, E., Grodensky, C. A., Rosen, D. L., Yuen, A., et al. (2012) · PubMed Central · Cited by 57 · see citing works
Fallahi, P., Ferrari, S. M., & Antonelli, A. (2016) · Endocrine · doi:10.1007/s12020-015-0836-y · Cited by 53 · see citing works
Levothyroxine absorption in health and disease, and new therapeutic perspectives.
Ianiro, G., Mangiola, F., Rienzo, T. A. D., Bibbò, S., Franceschi, F., Greco, A. V., & Gasbarrini, A. (2014) · PubMed · Cited by 51 · see citing works
Colucci, P., D'Angelo, P., Mautone, G., Scarsi, C., & Ducharme, M. P. (2011) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e318217b69f · Cited by 45 · see citing works
Self-citationCappelli, C., Castello, R., Marini, F., Paoletta, A., Marchetti, M., Saullo, M., Cristiano, A., Pirola, I., Gandossi, E., Ferlin, A., et al. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00699 · Cited by 43 · see citing works
Once weekly thyroxine treatment as a strategy to treat non-compliance
Rangan, S., Tahrani, A. A., Macleod, A. F., & Moulik, P. K. (2007) · Postgraduate Medical Journal · doi:10.1136/pgmj.2007.060244 · Cited by 42 · see citing works
Adherence to levothyroxine among patients with hypothyroidism in Lebanon
Helou, S. E., Hallit, S. R., Awada, S., Al‐Hajje, A., Rachidi, S., Bawab, W., Salameh, P., & Zein, S. (2018) · Eastern Mediterranean Health Journal · doi:10.26719/emhj.18.022 · Cited by 38 · see citing works
Thyroid hormone replacement: current status and challenges
Okosieme, O. E. (2011) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2011.600307 · Cited by 33 · see citing works
Tanguay, M., Girard, J., Scarsi, C., Mautone, G., & Larouche, R. (2019) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.608 · Cited by 33 · see citing works
Self-citationSkelin, M., Lucijanić, T., Liberati-Čizmek, A.-M., Klobučar, S. M., Lucijanić, M., Jakupović, L., Bakula, M., Lončar, J. V., Marušić, S., Matić, T., et al. (2018) · Endocrine · doi:10.1007/s12020-018-1686-1 · Cited by 31 · see citing works
Twice-weekly dosing for thyroxine replacement in elderly patients with primary hypothyroidism
Taylor, J., Williams, B. O., Frater, J., Stott, D. J., & Connell, J. (1994) · Journal of International Medical Research · doi:10.1177/030006059402200504 · Cited by 30 · see citing works
Juch, H., Lupattelli, A., Ystrøm, E., Verheyen, S., & Nordeng, H. (2016) · Patient Education and Counseling · doi:10.1016/j.pec.2016.04.006 · Cited by 30 · see citing works
Laurent, I., Tang, S., Astère, M., Wang, K. R., Deng, S., Xiao, L., & Li, Q. F. (2018) · Endocrine · doi:10.1007/s12020-018-1574-8 · Cited by 30 · see citing works
Bornschein, A., Paz-Filho, G., Graf, H., & de Carvalho, G. A. (2012) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302012000400006 · Cited by 28 · see citing works
Al-Numani, D., Scarsi, C., & Ducharme, M. P. (2016) · Int. Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cp202485 · Cited by 12 · see citing works
Self-citationTopaloğlu, Ö., Yavuz, A., & Aylıkcı, A. B. T. (2021) · International Journal of Clinical Practice · doi:10.1111/ijcp.14312 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [1]Pirahanchi Y, Toro F, Jialal I 2022 Physiology, Thyroid Stimulating Hormone. StatPearls, Treasure Island, FL. 29763025
Cited by
Sorted by citations
Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
The use of levothyroxine absorption tests in clinical practice
Caron, P., & Declèves, X. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad132 · Cited by 18 · see citing works
Liquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption
Gatta, E., Bambini, F., Buoso, C., Gava, M., Maltese, V., Anelli, V., Delbarba, A., Pirola, I., & Cappelli, C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1080108 · Cited by 13 · see citing works
Oteri, V., Volpe, S., Lopes, M., Sceusa, G., Tumminia, A., Belfiore, A., Frasca, F., & Gullo, D. (2024) · Endocrine · doi:10.1007/s12020-024-04016-7 · Cited by 9 · see citing works
Ruchała, M., Bossowski, A. T., Brzózka, M. M., Gietka‐Czernel, M., Hubalewska–Dydejczyk, A., Kos‐Kudła, B., Lewiñski, A., Syrenicz, A., & Zgliczyński, W. (2022) · Endokrynologia Polska · doi:10.5603/ep.a2022.0078 · Cited by 7 · see citing works
Changes in Drug Clinical Trials of Thyroid Diseases in China, 2009–2022
Li, C., Hao, J., Wang, C., Yang, J., Zheng, Y., Zhang, K., Wen, H., Meng, X., Gao, J., Li, W., et al. (2023) · Drug Design Development and Therapy · doi:10.2147/dddt.s409617 · Cited by 5 · see citing works
Beyond the Gut: thyroxine malabsorption, pharmacokinetics, and delivery
Law, L. S., Kuu, N. W. X., Leong, M. H. T., Lo, E. A. G., Yeoh, S. F., & Yang, S. P. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag024 · Cited by 2 · see citing works
Nuevas formulaciones de levotiroxina en el tratamiento del hipotiroidismo
Iglesias, P. (2023) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2023.11.001 · Cited by 2 · see citing works
Drug forms of levothyroxine. Is there room for innovation in hypothyroidism treatment?
Kolpakova, E. A., Voznesenskaya, А. А., Викторовна, Ф. Н., & Troshina, E. A. (2023) · Clinical and experimental thyroidology · doi:10.14341/ket12759 · Cited by 1 · see citing works
Comparison of tablet versus liquid ethanol-free Levothyroxine in thyroidectomised patients
Croce, L., Chytiris, S., Teliti, M., Bertini, J., Pizzuto, L., Molin, M. D., Limiroli, M., Calì, B., Magri, F., & Rotondi, M. (2025) · Endocrine · doi:10.1007/s12020-025-04375-9 · Cited by 1 · see citing works
New formulations of levothyroxine in the treatment of hypothyroidism
Iglesias, P. (2024) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2024.03.009
Abdullah, E. M., ElDeeb, A. M., Sultan, E. A., Ghareib, H. O., & EL-Badry, S. M. (2024) · Physiotherapy Quarterly · doi:10.5114/pq/173581
Xiao, Z., Li, Y., Wu, W., leong, H., Gan, L., Ye, W., Wang, T., Wu, C., Wang, W., & Pan, X. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.09.017
- Authors
- Ducharme, M., Scarsi, C., Bettazzi, E., Mautone, G., Lewis, Y., & Celi, F. S.
- Affiliations
- Université de Montréal (CA)
- IBSA Institut Biochimique (Switzerland) (CH)
- Learn and Confirm, Inc., St. Laurent, Quebec, Canada.
- Virginia Commonwealth University (US)
- Corresponding author
- Ducharme, Murray
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2022-08
- Volume
- 32
- Issue
- 8
- Pages
- 897-904
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- PMC
- PMC9419984
- OpenAlex
- W4224857493
- Cited by
- 13
- References
- 36
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Thyroid (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- levothyroxine, bioavailability, dietary intake, drug absorption, pharmacokinetics, hypothyroidism, medication adherence, healthy volunteers, bioequivalence, Cmax, Tmax
- MeSH terms
- Administration, Oral, Biological Availability, Female, Humans, Hypothyroidism, Male, Tablets, Thyroxine, Cross-Over Studies, Area Under Curve
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
