EXTENDED ABSORPTION OF LIOTHYRONINE FROM POLY-ZINC-LIOTHYRONINE (PZL) IN HUMANS

Background Liothyronine (LT3) has been increasingly used in combination with levothyroxine (LT4) in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical T3 peak seen after oral administration of LT3. Objectives To evaluate in healthy volunteers (i) the pharmacokinetics of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) monitoring for the adverse events; (iv) exploratory analysis of the sleep patterns after LT3, PZL or placebo administration. Methods 12 healthy volunteers 18 to 50 years of age were recruited for a Phase 1, double-blind, randomized, single-dose placebo-controlled, cross-over study to compare PZL against LT3 or placebo. Subjects were admitted three separate times to receive a randomly assigned capsule containing placebo, 50-mcg LT3, or 50-mcg-PZL, and were observed for 48h. A 2-week washout period separated each admission. Results LT3-derived serum T3 levels exhibited the expected profile, with a T max at 2h and return to basal levels by 24-36h. PZL-derived serum T3 levels exhibited a ∼30% lower Cmax that was 1 h delayed and extended into a plateau that lasted up to 6h. This was followed by a lower but much longer plateau; by 24 hours serum T3 levels still exceeded ½ of C max . TSH levels were similarly reduced indistinguishably in both groups. Conclusion PZL possesses the necessary properties to achieve a much improved T3 pharma-cokinetic. Drug product development of PZL should improve the delivery of T3 even further. PZL is on track to provide hypothyroid patients with stable levels of serum T3.