国产左甲状腺素钠片剂生物利用度研究

Study on the Relative Bioavailability of Levothyroxine Sodium Tablets in Healthy Volunteers

目的：采用开放随机原则对国产的两种规格（５０μｇ和１００μｇ）的左甲状腺素钠片与进口左甲状腺素钠片进行相对生物利用度及等效性检验研究，旨在观察片剂质量，为临床应用提供依据。方法：２１名健康男性受试者参加了单剂量（６００μｇ）三周期交叉试验并用放免分析法测定给药后不同时间点血清药物浓度。结果：试验药ＡＵＣ０－ｔ分别为 １０．１３±１．８４μｍｏｌ·ｈ－１·Ｌ－１和１０．３０±１．４２μｍｏｌ·ｈ－１·Ｌ－１，参比药ＡＵＣ０－ｔ为９．３７±１．２７μｍｏｌ·ｈ－１·Ｌ－１；试验药Ｃｍａｘ分别为１９７．５７±２７．４０ ｎｍｏｌ·Ｌ－１和１９１．１０±２７．３５ｎｍｏｌ．Ｌ－１，参比药 Ｃｍａｘ 为 １６９．４８± ２２．８３ ｎｍｏｌ·Ｌ－１。两种试验药的相对生物利用度为 １０７．３％和 １０９．９％，９０％可信限为 １０４．６％－１１０．０％和 １０５．９％～１１３．９％。结论：经方差分析和双单侧矿检验判断，提示国产的 ５０μｇ和 １００μｇ左甲状腺素钠片与进口左甲状腺素钠具有生物等效性。

OBJECTIVE: According to an open and randomized principle, the relative bioavailability of two kinds of domestic levothyroxine sodium tablets containing 50μg or 1OOμg were studied in comparison with imported levothyroxine sodium containing 100μg levothyroxine sodium. METHODS:2 1 healthy male volunteers received a single oral doses of 600μg of levothyroxine sodium in three times cross- over clinical trial and their serum drug concentration were determined by Radioimmunoassay (RIA). RESULTS: The results showed that the AUC0-t, values of studied medicine were 10.13±1.84 nmol.L-1 and 10.30±1.42 nmol.h.ml-1,the Cmax values were 197.57±27.40 nmol.L-1 and 191.10±27.35 nmol.L-1,respectively; the AUC0-t, and Cmax values of reference were 9.37±1.27 nmol.h.L-1 and 169.48±22.83 nmol.L-1 respectively. The relative bioavailability of 50μg levothyroxine sodium tablets was 107.3%, while 1OOμg was 109.9%, with a 90% confidence interval of 104.6%-110.0% and 1O5.9%-113.9% respectively. An analysis of variance and two one-sided t-test were performed to evaluate the bioequivalence of domestic and imported tablets. CONCLUSIONS: The results indicated that two domestic levothyroxine sodium preparations and levothyroxine sodium are bioequivalent.