BIOEQUIVALENCE OF 2 COMMERCIALLY AVAILABLE LEVOTHYROXINE-NA PREPARATIONS IN ATHYREOTIC PATIENTS

The thyroid hormones levothyroxine and levotriiodothyronine are vital for normal growth and development and play an important role in energy metabolism. The bioequivalence of levothyroxine following administrat ion of the test preparation (Eferox(R) 100 tablets, Wyeth Pharma GmbH, Munster Germany) and a reference preparation (each containing 100 mu g levothyroxine-Na, the sodium salt of the natural thyroxine isomer) w as investigated in 24 male and female patients with a lack of basal th yroid hormone secretion after an ablative thyroidectomy and postoperat ive radiotherapy. In a randomized, multicentric, open 3-factorial Lati n-square (2 x 2 x 2) crossover study the subjects received two pharmac eutical units of the formulations once daily in the morning 30 min bef ore breakfast during two periods of 35-42 consecutive days each. Serum concentrations of total thyroxine and total triiodothyronine were det ermined on screening day (basal concentrations), on the last 3 days of administration at predose to verify, steady-state conditions, and on the last day of administration at 9 predetermined time points up to 24 h postadministration to obtain 24-h hormone profiles. The two formula tions proved to be bioequivalent for levothyroxine regarding rate and extent of absorption. The bioequivalence decision was based on C-ss,C- max and AUD(0-24h).