A PILOT-STUDY ON THE DETERMINATION OF THE RELATIVE BIOAVAILABILITY OFLEVO-THYROXINE

A promising new design aimed at testing bioequivalence of levo-thyroxi ne preparations in male euthyreotic volunteers was investigated in a p ilot study Healthy volunteers received a single oral dose of levo-thyr oxine (200 mu g of the same formulation, 2 tablets of 100 mu g each) i n 4 subsequent periods with washout times of 1 week between administra tions. Consistent increases in serum levo-thyroxine concentrations wer e observed after intake of each dose. The number of volunteers include d, in our case 12, was sufficient to state bioequivalence of the medic ation given in 4 subsequent periods as assessed by area under data aft er substraction of area under basal levo-thyroxine concentrations dete rmined on the day before drug administration and allowed an estimate o f the minimum number required for future studies. Furthermore, combina tion of individual values from different periods of identical treatmen t may lead to a reduction of minimum sample size. The design rested co uld also be used as a crossover design to obtain a reliable parameter related to relative levothyroxine bioavailability and is a promising a lternative to another model where bioavailability cart be tested in at hyreotic patients. The medication was well tolerated and no adverse ev ents related to medication were found. Safety parameters failed to rev eal any marked change during the 4 study periods.