Department of Pharmacotherapy and Outcomes Sciences; Virginia Commonwealth University, Richmond, Virginia.
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Thyroid. 2019 Oct;29(10):1371-1379. doi: 10.1089/thy.2019.0101. Epub 2019 Sep 12.
L-triiodothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer (TC) patients during the preparation for nuclear medicine procedures, and it is used in combination with LT4 in patients who do not respond to the standard treatment for hypothyroidism. This therapy is commonly done by using fixed doses, potentially resulting in supraphysiologic levels of triiodothyronine (T3). A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes that are able to maintain serum T3 levels within the reference range, but data on the PK of LT3 are conflicting. Here, we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, and not receiving LT4 therapy. We performed an open-label, PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived TC. LT3 was substituted for LT4 at a 1:3 mcg/mcg dosage ratio thrice daily for at least 30 days. PK of the last LT3 dose while at steady state and terminal elimination was assessed over 11 days. Thereafter, a PK study was performed following the nuclear medicine procedure in patients who volunteered for a second study. Fourteen patients age 48.5 ± 16.0 years completed the last dose study and five completed the second PK study. PK analysis indicates a time to maximum serum concentration of 1.8 ± 0.32 hours and two distinct phases of linear elimination, with a fast distribution phase and slow elimination phases with half-lives of 2.3 ± 0.11 hours and 22.9 ± 7.7 hours, supporting a two-compartment model. PK modeling predicts that a twice-daily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the reference range. The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapies directed to maintain stable T3 serum levels.
三碘甲状腺原氨酸（LT3）是甲状腺癌（TC）患者在准备核医学程序时替代左甲状腺素（LT4）的药物，并且在对标准甲状腺功能减退症治疗无反应的患者中与 LT4 联合使用。这种治疗通常采用固定剂量，可能导致三碘甲状腺原氨酸（T3）的生理水平升高。为了设计能够将血清 T3 水平维持在参考范围内的联合治疗方案，需要对 LT3 的药代动力学（PK）有很好的了解，但关于 LT3 的 PK 数据存在争议。在这里，我们介绍了一项旨在描述在没有内源性甲状腺激素产生且未接受 LT4 治疗的患者中 LT3 PK 的研究。我们在因滤泡源性 TC 接受核医学程序评估和治疗而进行甲状腺激素停药的患者中进行了一项开放标签的 PK 研究。LT3 以 1:3mcg/mcg 的剂量比每天三次替代 LT4，至少 30 天。在稳定状态和终末消除期间评估最后一次 LT3 剂量的 PK 超过 11 天。此后，在自愿进行第二次研究的患者中进行核医学程序后进行 PK 研究。14 名年龄 48.5±16.0 岁的患者完成了最后一次剂量研究，5 名患者完成了第二次 PK 研究。PK 分析表明，血清浓度达峰时间为 1.8±0.32 小时，有两个线性消除阶段，快速分布阶段和缓慢消除阶段半衰期分别为 2.3±0.11 小时和 22.9±7.7 小时，支持二室模型。PK 建模预测，每日两次给予低剂量 LT3（0.07 mcg/kg 每日两次）与 LT4 联合使用，可以预测性地增加血清 T3 浓度，而不会出现明显高于参考范围的峰值。LT3 的 PK 很好地描述为二室模型，假设仅从采样室消除，具有快速分布阶段和缓慢消除阶段。这些信息将有助于设计 LT3/LT4 联合治疗的治疗策略，以维持稳定的 T3 血清水平。
