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

LT3-derived serum T3 levels exhibited the expected rapid absorption profile with peak concentration at 2 hours and return to basal levels by 24-36 hours.

• Tmax for LT3 was approximately 2 hours post-administration
• Serum T3 levels returned to basal levels by 24-36 hours after LT3 administration
• Single dose of 50 μg LT3 was administered in a capsule form
• Study design was a Phase 1, double-blind, randomized, single-dose placebo-controlled crossover study in 12 healthy volunteers aged 18-50 years

PZL-derived serum T3 levels showed approximately 30% lower Cmax compared to LT3, with peak concentration delayed by 1 hour.

• PZL Cmax was ~30% lower than LT3 Cmax
• Tmax for PZL was approximately 3 hours (1 hour delayed compared to LT3's 2-hour Tmax)
• The same molar dose of 50 μg was used for both PZL and LT3
• PZL is a metal coordinated form of LT3 (poly-zinc-liothyronine)

PZL produced an extended absorption profile characterized by a plateau lasting up to 6 hours followed by a prolonged lower plateau persisting to 24 hours.

• After reaching Cmax, PZL-derived T3 levels extended into a plateau that lasted up to 6 hours
• Following the initial plateau, a lower but much longer secondary plateau was observed
• By 24 hours, serum T3 levels from PZL still exceeded one-half of Cmax
• This extended profile contrasts sharply with LT3, which returned to basal levels by 24-36 hours

Thyrotropin (TSH) levels were similarly reduced in both the LT3 and PZL groups.

• TSH suppression was comparable between LT3 and PZL treatment arms
• TSH reduction served as a pharmacodynamic measure of T3 activity
• The similar TSH suppression indicates PZL-derived T3 was biologically active despite the lower Cmax
• Subjects were healthy volunteers observed over a 48-hour period with a 2-week washout between each of the three treatment arms

The study included an exploratory analysis of sleep patterns following LT3, PZL, or placebo administration.

• Sleep pattern monitoring was included as an exploratory endpoint in the Phase 1 study
• Three treatment conditions were compared: placebo, 50 μg LT3, and 50 μg PZL
• Subjects were admitted three separate times in a crossover design with 2-week washout periods separating each admission
• Subjects were observed for 48 hours following each dose administration

PZL had previously been shown in rats to avoid the typical T3 peak seen after oral administration of LT3.

• Animal studies in rats demonstrated that PZL avoided the typical triiodothyronine peak seen after oral LT3 administration
• The rat data provided the preclinical rationale for advancing PZL to a Phase 1 human study
• PZL is described as a metal coordinated form of LT3
• The human Phase 1 results confirmed the extended absorption profile suggested by the rat studies