Bioequivalence of two 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 administration of the test preparation (Eferox 100 tablets, Wyeth Pharma GmbH, Münster, Germany) and a reference preparation (each containing 100 micrograms levothyroxine-Na, the sodium salt of the natural thyroxine isomer) was investigated in 24 male and female patients with a lack of basal thyroid hormone secretion after an ablative thyroidectomy and postoperative radiotherapy. In a randomized, multicentric, open 3-factorial Latin-square (2 x 2 x 2) crossover study the subjects received two pharmaceutical units of the formulations once daily in the morning 30 min before breakfast during two periods of 35-42 consecutive days each. Serum concentrations of total thyroxine and total triiodothyronine were determined 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 formulations proved to be bioequivalent for levothyroxine regarding rate and extent of absorption. The bioequivalence decision was based on CSS,max and AUD0-24h.
Gottwald
R
R
Arbeitskreis klinische Arzneimittelprüfungen (AKP), Institut für klinische Pharmakologie Bobenheim, Grünstadt, Germany.
Lorkowski
G
G
Petersen
G
G
Schnitzler
M
M
Lücker
P W
PW
D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D018592:Cross-Over Studies; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D012015:Reference Standards; D013810:Therapeutic Equivalency; D013965:Thyroidectomy / Q000009:adverse effects; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000097:blood*; D044465:White People
D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine