Controlled Release of Liothyronine (LT3) Shown in First Clinical Trial of PolyZincLiothyronine (PZL)

Synthonics, Inc., a specialty pharmaceutical company focused on the development of proprietary metal coordinated pharmaceuticals, today announced the results of the first clinical trial of PolyZincLiothyronine (PZL), a novel extended release Liothyronine (LT3) compound for the management of hypothyroidism.   PZL is a copolymer of zinc and LT3 designed to slowly release T3 into the blood to provide patients the therapeutic benefits of LT3 without the side effects associated with the rapid absorption of currently available LT3 products. 

The trial compared the absorption of orally administered PZL with that of LT3 in a double-blind, randomized, placebo-controlled cross-over study of healthy individuals at the University of Chicago.   PZL demonstrated significantly better pharmacokinetics than LT3, with a controlled and extended release that more closely reflected the endogenous production of T3 by a healthy thyroid.  PZL produced a T3 Cmax 30% lower than LT3 and serum levels that remained near Cmax for about six hours before gradually declining to a level that exceeded one-half of Cmax at 24 hours.   “I am very encouraged by this demonstration of proof of concept and am confident that a PZL drug product can produce steady, euthyroid-like T3 levels with once daily use” said Dr. Thomas Piccariello, President and Chief Science Officer of Synthonics. 

There is a growing consensus within the medical community as to the benefits an extended release T3 could provide to hypothyroid patients that do not fully benefit from levothyroxine.  Dr. Scott Palmer, an assistant professor at Rush Medical College and the chairman of Synthonics’ scientific advisory board, stated that “a product, such as PZL, that provides stable replacement levels of T3 would represent a dramatic advance in the treatment of hypothyroidism and could significantly improve the health and quality of life of millions that suffer from that disease.”

A manuscript describing the study has been prepared by Drs. Alexandra Dumitrescu, Antonio Bianco and colleagues at the University of Chicago.  The manuscript will soon enter the peer review process and is available at medRciv (

About PZL:  Synthonics developed PZL, a proprietary copolymer of zinc and LT3, in response to a recommendation in the 2014 American Thyroid Association Guidelines for the Treatment of Hypothyroidism.  When administered orally, PZL is designed to adhere to the lining of the small intestine where it creates a depot of drug product from which T3 molecules are gradually released and absorbed into the bloodstream.  The gradual release of T3 molecules significantly reduces the peaks in circulating T3 levels produced by existing LT3 formulations and produce steady, euthyroid-like T3 levels in the blood of patients with hypothyroidism.  Preclinical proof of principle studies were conducted at Rush University Medical Center under the direction of Dr. Antonio C. Bianco (Thyroid 2018 Nov;28(11):1425-1433. doi: 10.1089/thy.2018.0205).   

About Hypothyroidism:  Hypothyroidism, a chronic condition that affects approximately fifteen million Americans, occurs when the thyroid fails to produce adequate quantities of thyroid hormones.  Patients with hypothyroidism typically take levothyroxine (LT4), a prohormone that the body converts to T3, the active hormone that controls metabolism.  A significant subset of the hypothyroid population, however, fails to respond fully to LT4 administration and continues to suffer from symptoms such as fatigue, impaired cognition and weight gain.  Studies of large groups of patients with hypothyroidism indicate that even patients that are otherwise asymptomatic on LT4 exhibit impaired memory and report poor quality of life as compared to age-matched control from the general population.

Administration of LT3 could materially improve subjective and objective health parameters for the population of patients with hypothyroidism that remain symptomatic on LT4. The available data from double blinded clinical trials indicate preference for therapy that contains LT3. But the possible adverse effects, such as palpitation and tightness of the chest, which have been associated with the rapid absorption and clearance rates of conventional LT3 products limit their broader clinical use.  PZL is designed to address those issues and provide steady blood T3 levels like those produced by a healthy thyroid gland. 

About Synthonics:  Synthonics is a specialty pharmaceutical company focused on the discovery and development of metal coordinated pharmaceuticals (“MCP’s”).  Metal coordination entails attaching a metal, such as magnesium, zinc or bismuth, to a known drug to improve that drug’s pharmacokinetics, performance and safety.  MCP’s of approved drugs are both patentable as new compositions of matter and eligible for FDA review under 505(b)(2). 

For further information, contact John Tinkham, CEO of Synthonics, at

The National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health has provided funding for the clinical trial under Award Number R44DK116396. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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