A new method for the determination of the bioavailability of thyroid hormone preparations

Levothyroxine and levotriiodothyronine are vital hormones that are produced and stored in the thyroid gland. Due to endogenic hormone production and regulation, it is impossible to determine the bioavailability of exogenic hormone using conventional trial designs since exogenic hormone cannot be distinguished from endogenic hormone in serum unless radiolabelled. Bioavailability, however, is an essential quality attribute of thyroid hormone preparations. A new trial design was developed that allows the bioavailability of thyroid hormone preparations to be determined without the use of radiolabelled substances. The trial subjects were volunteers (athyreotic patients) who, after thyroidectomy and postoperative radioiodine therapy, do not produce endogenic thyroid hormone and have to be supplied with exogenic levothyroxine on a permanent basis (replacement therapy). An oral solution of levothyroxine was used as a reference. Such a solution can be prepared with the same biopharmaceutical quality on a reproducible basis and is suitable for comparing preparations with one another that are used in different trials with the same design. The orally given reference solution is well tolerated and can therefore be administered over the required periods of time (e.g., 3 x 4 weeks). In a randomized, 3-way Latin-square design, the volunteers were given either L-Thyroxin Henning, another tablet preparation, or the reference solution, each for 28 days running during each period. On days 26, 27 and 28 of each period, the serum concentrations of levothyroxine and levotriiodothyroine were determined in order to verify the steady state.(ABSTRACT TRUNCATED AT 250 WORDS)