Young W F, Gorman C A, Jiang N S, Machacek D, Hay I D
Clin Pharmacol Ther. 1984 Dec;36(6):781-7. doi: 10.1038/clpt.1984.257.
Studies have shown that pharmaceutic preparations of the stereo isomers of thyroxine differ with respect to thyromimetic potency and lipid level-lowering effects. We applied a stereospecific assay for dextrothyroxine (DT4) and levothyroxine (LT4) to determine whether the biologic effects observed after the administration of DT4 (Choloxin; Flint Laboratories) resulted from inherent biologic activity of DT4, conversion of DT4 to LT4 in vivo, or LT4 contamination of Choloxin tablets. Choloxin was administered in a dose of 8 mg/day for 5 mo to nine athyreotic subjects who were then treated with pharmaceutic LT4 (Synthroid), 0.2 mg/day for an additional 5 mo. Analysis showed that LT4 contamination of Choloxin tablets ranged from 0.50% to 2.30%. This degree of contamination resulted in physiologically significant doses of LT4 in the 8 mg/day doses of Choloxin. During the treatment with two different lots of Choloxin, serum LT4 accounted for 33% to 53% of the measurable serum total thyroxine. The degree of LT4 contamination in Choloxin tablets was sufficient to account for the observed serum LT4 levels and casts doubt on the conclusions derived from previous studies in which Choloxin was used as the source of "DT4."
研究表明，甲状腺素立体异构体的药物制剂在甲状腺模拟效力和降低血脂水平的作用方面存在差异。我们应用了一种针对右旋甲状腺素（DT4）和左旋甲状腺素（LT4）的立体特异性测定法，以确定给予DT4（Choloxin；弗林特实验室）后观察到的生物学效应是源于DT4的固有生物活性、DT4在体内转化为LT4，还是Choloxin片剂中LT4的污染。以每天8毫克的剂量给9名甲状腺切除的受试者服用Choloxin，持续5个月，然后再用药物LT4（左旋甲状腺素钠片）以每天0.2毫克的剂量治疗5个月。分析表明，Choloxin片剂中LT4的污染范围为0.50%至2.30%。这种污染程度导致在每天8毫克剂量的Choloxin中含有生理上显著剂量的LT4。在用两批不同的Choloxin治疗期间，血清LT4占可测量血清总甲状腺素的33%至53%。Choloxin片剂中LT4的污染程度足以解释观察到的血清LT4水平，并对以前使用Choloxin作为“DT4”来源的研究得出的结论产生怀疑。
