Trantow T, Herzog R, Fuder H, Ise J, Lücker P W
Henning Berlin GmbH, Berlin, Germany.
Methods Find Exp Clin Pharmacol. 1995 Jun;17(5):333-43.
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.
一项初步研究对一种旨在测试左甲状腺素制剂在男性甲状腺功能正常志愿者体内生物等效性的新设计进行了调查。健康志愿者在随后的4个阶段接受单次口服剂量的左甲状腺素（200微克相同制剂，每片100微克，共2片），给药间隔的洗脱期为1周。每次服药后均观察到血清左甲状腺素浓度持续升高。我们纳入的志愿者人数为12名，这足以说明在减去给药前一天测定的基础左甲状腺素浓度下的数据面积后，后续4个阶段给药的药物生物等效性，并可估计未来研究所需的最小样本量。此外，将相同治疗不同阶段的个体值相结合可能会减少最小样本量。所测试的设计也可用作交叉设计，以获得与左甲状腺素相对生物利用度相关的可靠参数，并且是另一种可在甲状腺功能减退患者中测试生物利用度的模型的有前景的替代方案。该药物耐受性良好，未发现与药物相关的不良事件。安全参数在4个研究阶段未显示任何明显变化。
