ABSTRACT
Objective: Levothyroxine is essential for the treatment of hypothyroidism, but unfortunately its absorption when taken as a tablet has been shown to be significantly decreased with coffee or food ingestion, particularly if containing calcium or magnesium. Tablets and soft-gel formulations of levothyroxine are therefore recommended to be taken at least 30 minutes before meals, an inconvenience for patients in the morning. Tirosint-Sol® is a novel solution of levothyroxine that has been shown to result in an approximate 30 minutes faster absorption process than tablets or soft gel formulations. The objective of this trial was to investigate whether Tirosint-Sol® could be administered as late as 15 minutes before a high-fat, high-caloric meal, in comparison to 30 minutes. Methods: Thirthy-six (thirty-three completers, 24 males and 9 females) healthy volunteers participating in the randomized study took a 600 mcg Levothyroxine dose of Tirosint-Sol® after a 10-hour fast, 15 or 30 minutes before a high-fat high-caloric “FDA type” breakfast. Serum samples were taken at three different times at baseline, and at 0.5, 1, 1.5, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and at 72 hours after dosing. The washout period was at least 35 days. Serum concentrations of Levothyroxine were measured using a validated LC-MS method. Results: Median tmax was unchanged between the two groups at 1.5 h. The three subjects that did not complete the trial did so because of not showing up for COVID19 testing, vomiting within 6 hours after dosing, and not finishing the breakfast. The geometric mean ratios and confidence intervals for the baseline adjusted maximum (Cmax, 85%, CI: 80-90%) and extent of exposure (AUC0-72, 92%, CI: 87-97%) were within the recognized equivalence boundaries of 80 to 125%, indicating an absence of meaningful clinical difference between dosing at 15 or 30 minutes before a meal. There were no differences in adverse events between groups. Discussion/Conclusion: The data of this randomized study indicate that the absorption profile of Tirosint-Sol® is clinically equivalent when administered 30 or 15 minutes before a high-fat high-caloric breakfast.