A pilot study on the determination of the relative bioavailability of levo-thyroxine.
A promising new design aimed at testing bioequivalence of levo-thyroxine preparations in male euthyreotic volunteers was investigated in a pilot study. Healthy volunteers received a single oral dose of levo-thyroxine (200 micrograms of the same formulation, 2 tablets of 100 micrograms each) in 4 subsequent periods with washout times of 1 week between administrations. Consistent increases in serum levo-thyroxine concentrations were observed after intake of each dose. The number of volunteers included, in our case 12, was sufficient to state bioequivalence of the medication given in 4 subsequent periods as assessed by area under data after subtraction of area under basal levo-thyroxine concentrations determined on the day before drug administration, and allowed an estimate of the minimum number required for future studies. Furthermore, combination of individual values from different periods of identical treatment may lead to a reduction of minimum sample size. The design tested could also be used as a crossover design to obtain a reliable parameter related to relative levo-thyroxine bioavailability and is a promising alternative to another model where bioavailability can be tested in athyreotic patients. The medication was well tolerated and no adverse events related to medication were found. Safety parameters failed to reveal any marked change during the 4 study periods.
Trantow
T
T
Henning Berlin GmbH, Berlin, Germany.
Herzog
R
R
Fuder
H
H
Ise
J
J
Lücker
P W
PW
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D004334:Drug Administration Schedule; D005858:Germany; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011863:Radioimmunoassay; D012016:Reference Values; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D013974:Thyroxine