Cooper D S, Kieffer J D, Saxe V, Mover H, Maloof F, Ridgway E C
Endocrinology. 1984 Mar;114(3):786-93. doi: 10.1210/endo-114-3-786.
Methimazole [1-methyl-2-mercaptoimidazole (MMI)] was given to normal male rats in their drinking water in concentrations ranging from 0.0001-0.05% for either 1 week or 1 month. Serum MMI levels in the rats ranged from 0.008-19.6 micrograms/ml, and were similar after 1 week and 1 month of treatment. Serum MMI was linearly related to the MMI concentration in the drinking water (r = 0.98, P less than 0.001). In contrast, intrathyroid MMI content plateaued with increasing MMI concentrations in the water, and was linearly related to the logarithm of the MMI concentration. At the highest MMI concentration (0.05%), thyroid MMI contents were similar in the 1-week and 1-month groups (approximately 1 X 10(-4) M). Surprisingly, at lower MMI concentrations, thyroid MMI content was significantly higher in the 1-week group than the 1-month group. Thyroid function was inhibited by MMI with similar depression of serum T4 or T3 after 1 week or 1 month of MMI treatment. Although the MMI concentration for 50% suppression of thyroid PBI was 0.003% in both groups, thyroid MMI content at this MMI concentration was 97 microM after 1 week but only 15 microM after 1 month. The continued thyroid-inhibiting activity of MMI at 1 month, despite a striking decrease in thyroid MMI content, may relate to intrathyroid iodide depletion, which was more severe after 1 month (thyroid 127I = 40 microM) than after 1 week (thyroid 127I = 140 microM) or in controls (470 microM). Rats were given 0.05% MMI for either 1 week or 1 month, and the drug was then withdrawn. In the 1-week group, serum MMI disappeared biexponentially, with a rapidly declining phase (t1/2 = 3.2 h) and a second, slower disappearance phase (t1/2 = 47.7 h). Similar findings were noted after 1 month of treatment. The disappearance of thyroid MMI was also biexponential after 1 week, but this variable could not be evaluated after 1 month because thyroid MMI fell rapidly to undetectable levels. There was a highly significant correlation in the 1-week group between the disappearance of MMI from the thyroid and the recovery of thyroid function as assessed by thyroid PBI (r = 0.81, P less than 0.01). Despite the very rapid disappearance of MMI from the thyroid after 1 month of treatment, the recovery time of thyroid PBI was significantly longer than after 1 week of treatment (2.1 days vs. 1.4 days for 50% recovery, P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
将甲巯咪唑[1-甲基-2-巯基咪唑（MMI）]以0.0001 - 0.05%的浓度添加到正常雄性大鼠的饮用水中，持续1周或1个月。大鼠血清中的MMI水平在0.008 - 19.6微克/毫升之间，治疗1周和1个月后的水平相似。血清MMI与饮用水中MMI浓度呈线性相关（r = 0.98，P < 0.001）。相比之下，甲状腺内的MMI含量随着水中MMI浓度的增加而趋于平稳，并与MMI浓度的对数呈线性相关。在最高MMI浓度（0.05%）时，1周组和1个月组的甲状腺MMI含量相似（约1×10⁻⁴ M）。令人惊讶的是，在较低的MMI浓度下，1周组的甲状腺MMI含量显著高于1个月组。MMI抑制甲状腺功能，在MMI治疗1周或1个月后，血清T4或T3有类似程度的降低。虽然两组中抑制甲状腺蛋白结合碘（PBI）50%的MMI浓度均为0.003%，但在此MMI浓度下，1周后甲状腺MMI含量为97微摩尔，而1个月后仅为15微摩尔。尽管1个月时甲状腺MMI含量显著下降，但MMI在1个月时仍具有持续的甲状腺抑制活性，这可能与甲状腺内碘耗竭有关，1个月后的碘耗竭（甲状腺¹²⁷I = 40微摩尔）比1周后（甲状腺¹²⁷I = 140微摩尔）或对照组（470微摩尔）更严重。给大鼠服用0.05%的MMI 1周或1个月，然后停药。在1周组中，血清MMI呈双指数消失，有一个快速下降阶段（t1/2 = 3.2小时）和第二个较慢的消失阶段（t1/2 = 47.7小时）。治疗1个月后也有类似发现。1周后甲状腺MMI的消失也是双指数的，但1个月后无法评估该变量，因为甲状腺MMI迅速降至无法检测的水平。在1周组中，甲状腺内MMI的消失与通过甲状腺PBI评估的甲状腺功能恢复之间存在高度显著的相关性（r = 0.81，P < 0.01）。尽管治疗1个月后MMI从甲状腺中非常迅速地消失，但甲状腺PBI的恢复时间显著长于治疗1周后（50%恢复时分别为2.1天和1.4天，P < 0.01）。（摘要截取自400字）
