Extended Absorption of Liothyronine from Poly-Zinc-Liothyronine: Results from a Phase 1, Double-Blind, Randomized, and Controlled Study in Humans
Extended Absorption of Liothyronine from Poly-Zinc-Liothyronine: Results from a Phase 1, Double-Blind, Randomized, and Controlled Study in Humans
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DOI：
10.1089/thy.2021.0304
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发表时间：
2021-12-31
期刊：
影响因子：
6.6
通讯作者：
Bianco, Antonio C.
中科院分区：
文献类型：
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作者：
Dumitrescu, Alexandra M.;Hanlon, Erin C.;Bianco, Antonio C.
背景：L-三碘甲状腺原氨酸（LT 3）与左旋甲状腺素联合治疗甲状腺功能减退症的应用越来越多。LT 3的一种金属配位形式，称为聚锌碘甲腺原氨酸（PZL），避免了大鼠口服LT 3后观察到的典型三碘甲腺原氨酸（T3）峰。目的：在健康志愿者中评价（i）单次给药后PZL衍生T3的药代动力学（PK），（ii）PZL衍生T3的药效学，（iii）不良事件的发生率，和（iv）探索性分析LT 3、PZL或安慰剂（PB）给药后的睡眠模式。方法：招募12名18-50岁的健康志愿者进行1期、双盲、随机、单剂量PB对照、交叉研究，以比较PZL与LT 3或PB。受试者分别入院三次，接受随机分配的含有PB、50 μ g LT 3或50 μ g PZL的胶囊，并观察48小时。每次入院间隔2周的洗脱期。结果：LT 3衍生的血清T3水平表现出预期的曲线，Tmax为2小时，24-36小时恢复到基础水平。PZL衍生的血清T3水平表现出类似于30%的C-max降低，延迟1小时并延长至持续长达6小时的平台期。随后是较低但更长的平台期;到24小时，血清T3水平仍超过C-max的1/2。促甲状腺激素水平在两个groups.Conclusion类似减少：PZL具有必要的属性，以实现大大改善T3 PK。PZL有望为甲状腺功能减退患者提供稳定的血清T3水平。
Background: L-triiodothyronine (LT3) has been increasingly used in combination with levothyroxine in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical triiodothyronine (T3) peak seen after oral administration of LT3.Objectives: To evaluate in healthy volunteers (i) the pharmacokinetics (PK) of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) incidence of adverse events, and (iv) exploratory analysis of the sleep patterns after LT3, PZL, or placebo (PB) administration.Methods: Twelve healthy volunteers 18-50 years of age were recruited for a Phase 1, double-blind, randomized, single-dose PB-controlled, crossover study to compare PZL against LT3 or PB. Subjects were admitted three separate times to receive a randomly assigned capsule containing PB, 50 mu g LT3, or 50 mu g PZL, and were observed for 48 hours. A 2-week washout period separated each admission.Results: LT3-derived serum T3 levels exhibited the expected profile, with a T-max at 2 hours and return to basal levels by 24-36 hours. PZL-derived serum T3 levels exhibited similar to 30% lower C-max that was 1 hour delayed and extended into a plateau that lasted up to 6 hours. This was followed by a lower but much longer plateau; by 24 hours serum T3 levels still exceeded 1/2 of C-max. Thyrotropin levels were similarly reduced in both groups.Conclusion: PZL possesses the necessary properties to achieve a much improved T3 PK. PZL is on track to provide hypothyroid patients with stable levels of serum T3.