Comparative bioavailability of different formulations of levothyroxine and liothyronine in healthy volunteers
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Objective. To evaluate the relative bioavailability of T4 sodium 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 T4 or 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 T4 and 20μg (1 ml or 1 tablet) of T3 were administered with an open, randomized, crossover design. T4 and T3 serum 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−t was 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−t was 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−t and 0.99 for Cmax. Study 2: after administration of T3-lbsa oral solution, Cmax was 3.19± 0.25 ng/ml, AUC0−t was 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.
Key-wordsBioavailability levothyroxine liothyronine lioequivalence formula