Comparative bioavailability of different formulations of levothyroxine and liothyronine in healthy volunteers.
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-Ibsa and T3-Ibsa, respectively) were compared to two reference drugs, ie Eutirox 100 and Ti-tre tablets, respectively. A single oral dose of 100 microg (1 ml or 1 tablet) of T4 and 20 microg (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 in electro-chemo-luminescence method.


RESULTS
Study 1: after administration of T4-Ibsa oral solution, Cmax was 14.26+/-0.61 microg/dl, AUC0-t was 282.70 +/-14.29 microg/dl/h, Tmax was 2.71+/-0.25 h. After administration of Eutirox 100 tablets, Cmax was 14.34+/-0.59 microg/dl, AUC0-t was 279.42+/-9.59 microg/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-Ibsa 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-t was 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-t and 1.01 for Cmax.


CONCLUSIONS
The bioavailability of the two oral solutions (T4-Ibsa and T3-Ibsa oral solutions) and the corresponding tablet forms (Eutirox 100 and Ti-tre tablets) were confirmed and they can be considered bioequivalent and therapeutically interchangeable.
Leggio
G M
GM
Department of Experimental and Clinical Pharmacology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Incognito
T
T
Privitera
G
G
Marano
M R
MR
Drago
F
F
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012996:Solutions; D013607:Tablets; D013974:Thyroxine / Q000097:blood / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000097:blood / Q000493:pharmacokinetics*
D012996:Solutions; D013607:Tablets; D014284:Triiodothyronine; D013974:Thyroxine