Chemical structure of thyroxine
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Liothyronine

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the active T3 within cells by deiodinases. These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). more...

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Circulation

Most of the thyroid hormone circulating in the blood is bound to transport proteins :

  • Thyroxine-binding globulin (TBG)
  • Thyroid-binding prealbumin (TBPA) - this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR)
  • albumin.

Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. This free fraction is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. These values are referred to as fT4 and fT3. Another critical diagnostic tool is the amount of thyroid-stimulating hormone that is present. When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

Function

The thyronines act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline).The thyroid hormones are essential to proper development and differentiation of all cells of the human body. To various extents, they regulate protein, fat and carbohydrate metabolism. But they have their most pronounced effects on how human cells use energetic compounds. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

The thyronamines function via some unknown mechanism to inhbit neuronal activity; this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a severe drop in body temperature.

Related diseases

Both excess and deficiency of thyroxine can cause disorders.

  • Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.
  • Hypothyroidism is the case where there is a deficiency of thyroxine.

Medical use of thyroid hormones

Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine, the most commonly used form, is a stereoisomer of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration.

Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock.

Read more at Wikipedia.org


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West Pharmaceutical Services and T3 Therapeutics Announce Collaborative Agreement to Develop Oral Sustained Release Liothyronine
From Business Wire, 5/29/03

Business Editors/Health/Medical Writers

LIONVILLE, Pa. and MANHASSETT, N.Y.--(BUSINESS WIRE)--May 29, 2003

West Pharmaceutical Services, Inc. (NYSE: WST) and T3 Therapeutics LLC today announced that they have signed a worldwide licensing agreement for the development and commercialization of an oral sustained release formulation of liothyronine (T3), used for the treatment of congestive heart failure and hypothyroidism.

Liothyronine is a naturally occurring hormone produced by the thyroid gland that is deficient in patients with congestive heart failure and with hypothyroidism, where it often causes cardiovascular disease. Currently, liothyronine is taken orally by patients suffering from hypothyroidism. According to the American Thyroid Association, hypothyroidism can lead to the buildup of cholesterol in the vascular system and can cause plaque (hardening of the arteries), which can increase the risk of heart attack.

"Our agreement with West Pharmaceutical Services marks an important milestone in realizing our goal to develop formulations of liothyronine (T3) for the treatment of cardiovascular and endocrine diseases," said Dr. Irwin Klein, President of T3 Therapeutics LLC.

Despite their popularity, traditional oral delivery systems are not without problems. For example, the oral delivery of some drugs is associated with relatively poor drug bioavailability and highly variable blood drug levels, thereby requiring multiple dosing, which can compromise cost effectiveness and patient compliance. West's innovative formulation technologies are used to regulate the oral delivery of pharmaceuticals, allowing for the controlled release of the drug into the blood stream. In the case of hypothyroidism, the precise amount of liothyronine released into the bloodstream has a significant effect on the patient's therapeutic benefit.

According to Dr. Bruce Morra, President of West's Drug Delivery Systems Division, "Our collaboration with T3 Therapeutics builds on West's considerable expertise in formulation development of dosage forms and complements our solid base in nasal delivery technologies, bioanalytical evaluation and analytical development. Although it is in its early stages, we believe this program, if successful, can lead to improved therapies for millions of patients worldwide."

About West Pharmaceutical Services Drug Delivery Systems Division

West Pharmaceutical Services Drug Delivery Systems Division provides clients with the science, engineering and know-how necessary to take pharmaceutical products to the market. West's innovative product development has led to significant proprietary technologies in nasal formulations for systemic or local delivery, advanced oral delivery systems, transmucosal vaccine delivery and parenteral drug delivery.

Additionally, West supports its clients in all aspects of pharmaceutical development, from initial feasibility studies to formulation optimization and product development. For more information visit www.westdrugdelivery.com.

About T3 Therapeutics Corporation

T3 Therapeutics LLC is an early stage biopharmaceutical company dedicated to the development of thyroid hormone based therapies for human disease states. T3 Therapeutics has identified the potential for and currently holds a U.S. patent for T3 based therapies for heart failure and for the over 20 million patients with hypothyroidism currently being treated with T4 alone.

About West Pharmaceutical Services

West Pharmaceutical Services, Inc. (NYSE: WST) is a global drug delivery technology company that applies proprietary materials science, formulation research and manufacturing innovation to advance the quality, therapeutic value, development speed and rapid market availability of pharmaceuticals, biologics, vaccines and consumer healthcare products. West is the world's premiere provider of standard-setting systems and device components for parenterally administered medicines and an emerging leader in the development of advanced formulation technologies for the transmucosal delivery of drugs. Internationally headquartered in Lionville, Pennsylvania, West supports its partners and customers from 50 locations throughout North America, South America, Europe, Mexico, Japan, Asia and the Pacific and Australia. For more information visit West at www.westpharma.com.

Cautionary Statement Regarding Forward-Looking Information

Certain statements contained in this Report or in other company documents and certain statements that may be made by management of the Company orally may contain forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. These statements can be identified by the fact that they do not relate strictly to historic or current facts. They use words such as "estimate," "expect," "intend," "believe," "plan, " "anticipate" and other words and terms of similar meaning in connection with any discussion of future operating or financial performance or condition. In particular, these include statements concerning future actions, future performance or results of current and anticipated products, sales efforts, expenses, the outcome of contingencies such as legal proceedings, and financial results.

Because actual results are affected by risks and uncertainties, the Company cautions investors that actual results may differ materially from those expressed or implied in any forward-looking statement.

It is not possible to predict or identify all such risks and uncertainties, but factors that could cause the actual results to differ materially from expected and historical results include, but are not limited to: sales demand, timing of customers' projects; successful development of proprietary drug delivery technologies and systems; regulatory, licensee and/or market acceptance of products based on those technologies; competitive pressures; the strength or weakness of the U.S. dollar; inflation; the cost of raw materials; the availability of credit facilities; and, statutory tax rates. With respect to the explosion and fire at the Company's Kinston, NC plant, the following factors should also be taken into consideration: the timely replacement of production capacity; the adequacy and timing of insurance recoveries for property losses; the unpredictability of existing and future possible litigation related to the explosion and the adequacy of insurance recoveries for costs associated with such litigation; government actions or investigations affecting the Company; the ability of the Company to successfully shift production and compounding capacity to other plant sites in a timely manner, including the successful integration of experienced personnel to other production sites; the extent of uninsured costs for, among other things, legal and investigation services and incremental insurance; and regulatory approvals and customer acceptance of goods from alternate sites.

The Company assumes no obligation to update forward-looking statements as circumstances change. Investors are advised, however, to consult any further disclosures the Company makes on related subjects in the Company's 10-K, 10-Q and 8-K reports.

COPYRIGHT 2003 Business Wire
COPYRIGHT 2003 Gale Group

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