Comparative bioavailability of different formulations of levothyroxine and liothyronine in healthy volunteers

Objective.To evaluate the relative bioavailability of T4sodium and liothyronine sodium (T3), administered in single doses as oral solution (drops) and tablet forms, according to two separate study protocols. Methods.Twenty-four healthy, male volunteers were included in both studies. Two test drugs containing T4or T3(T4-lbsa and T3-lbsa, respectively) were compared to two reference drugs, ie Eutirox 100 and Ti-tre tablets, respectively. A single oral dose of 100 μg (1 ml or 1 tablet) of T4and 20μg (1 ml or 1 tablet) of T3were administered with an open, randomized, crossover design. T4and T3serum concentrations were determined by a validated immunoassay inelectro-chemo-luminescence method. Results.Study 1: after administration of T4-lbsa oral solution, Cmax was 14.26± 0.61 μg/dl, AUC0−twas 282.70 ±14.29 μg/dl/h, Tmax was 2.71 ± 0.25 h. After administration of Eutirox 100 tablets, Cmax was 14.34± 0.59 μg/dl, AUC0−twas 279.42± 9.59 μg/dl/h and Tmax was 2.65± 0.23 h. The 90% confidence interval ratios between test/reference drugs were 1.01 for AUC0−tand 0.99 for Cmax. Study 2: after administration of T3-lbsa oral solution, Cmax was 3.19± 0.25 ng/ml, AUC0−twas 44.79± 2.15 ng/ml/h and Tmax was 2.31 ± 0.25 h. After administration of Ti-tre tablets, Cmax was 3.16± 0.23 ng/ml, AUC0−twas 45.19± 2.19 ng/ml/h and Tmax was 2.44± 0.34 h. The 90% confidence interval ratios between test /reference drugs were 0.99 for AUC0−tand 1.01 for Cmax. Conclusions.The bioavailability of the two oral solutions (T4-lbsa and T3-lbsa oral solutions) and the corresponding tablet forms (Eutirox 100 and Ti-tre tablets) were confirmed and they can be considered bioequivalent and therapeutically interchangeable.