Extended Absorption of Liothyronine from Poly-Zinc-Liothyronine: Results from a Phase 1,Double-Blind,Randomized,and Controlled Study in Humans

Abstract

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 μg LT3, or 50 μg 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 ∼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 ½ 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.