Comparative Bioavailability of a Novel Solution and a Tablet Formulation of Levothyroxine

Abstract

AbstractLevothyroxine (LT4) is the standard of care for treating hypothyroidism. Despite the established efficacy of LT4, 50% of treated patients fail to achieve normal thyrotropin levels. Oral formulations of LT4 that bypass the gastric phase of dissolution may offset some of the therapeutic shortcomings observed with tablets. An oral solution of LT4 can be administered to patients who are unable to swallow tablets; allows flexibility to individualize dosing; and may mitigate interference with LT4 absorption caused by food, coffee, increased gastric pH from atrophic gastritis, and malabsorption from bariatric surgery. The bioavailability of a novel LT4 oral solution and a reference LT4 tablet were compared in a randomized, laboratory‐blinded, single‐dose, 2‐period, 2‐sequence, crossover study in healthy euthyroid subjects. A single 600‐μg oral dose of LT4 solution (30 mL × 100 μg/5 mL) or tablet (2 × 300‐μg tablet) was administered under fasting conditions in each study period, and total thyroxine concentrations were measured for 72 hours after administration. The ratio of geometric least‐squares means and 90% confidence intervals for area under the concentration‐time curve from time 0 to 72 hours and maximum plasma concentration were calculated. Among 42 subjects in the pharmacokinetic population, the geometric least‐squares mean ratio of area under the concentration‐time curve from time 0 to 72 hours and maximum plasma concentration for baseline‐adjusted thyroxine was 109.1% and 107.9%, respectively, meeting Food and Drug Administration bioequivalence criteria. Adverse events (AEs) were similar between treatment groups with no serious AEs or discontinuations for AEs. Comparable bioavailability was observed between the LT4 oral solution and reference tablet after a single oral 600‐μg dose under fasting conditions.