Thyroid hormone natural preparations

Within a programme aimed at the development of thyroid hormone analogues as potentially useful plasma cholesterol-lowering agents, the pyrida-zinone derivative SK F L-94901 (98) has been prepared and investigated in the U.K. [419-422]. Whereas naturally occurring thyroid hormones cannot be employed for this purpose because of their undesirable effect on heart rate, (98) has been found to represent a potent thyromimetic which retains hepatic activity but lacks cardiac activity. Structural modifications and QSAR studies have been carried out [422]. 

Q76 Levothyroxine sodium is the synthetically prepared sodium salt of the natural isomer of thyroid hormone. Levothyroxine sodium tablets are unstable and require administration on an empty stomach. 

Levothyroxine sodium (Levothwid, Synthroid, Levoxine) is the sodium salt of the naturally occurring levorota-tory isomer of T4. It is the preparation of choice for maintenance of plasma T4 and T3 concentrations for thyroid hormone replacement therapy in hypothyroid patients. It is absorbed intact from the gastrointestinal tract, and its long half-life allows for convenient once-daily administration. Since much of the T4 is deiodi-nated to T3, it is usually unnecessary to use more expensive preparations containing bothX4 and Tj.The aim is to establish euthyroidism with measured serum concentrations of T4, T3, and TSH within the normal range. 

The synthetic preparations used are the sodium salts of the natural isomers of the thyroid hormones. Levothyroxine sodium (L-T, synthroid, levoxyl, levothroid, unithroid, others) is available in tablets in a variety of doses and as a lyophilized powder for injection. L-T has a narrow therapeutic index, and the FDA has mandated demonstration of bioequivalence for brand and generic preparations by the various producers. Liothyronine sodium (L-Tft is available in tablets (cytomel) and in an injectable form (triostat). A mixture of L-T and L-T is marketed as liotrix (thyroiar). Desiccated thyroid preparations, derived from whole animal thyroids and containing both T and T have highly variable biologic activity and are much less desirable. 

Thyroid hormone preparations belong to two categories natural hormone preparations derived from animal thyroid, and synthetic preparations. 

Natural preparations include desiccated thyroid and thyrogiobuiin. Desiccated thyroid and thyrogiobuiin are derived from thyroid glands of domesticated animals that are used for food by human. The hormones were released from the proteolytic activity of gut enzymes. Potency is based on total iodine content or bioassay and is somewhat variable with different preparations. 

Any of the commercially available thyroid preparations accomplish this goal (Table 73-8) however, levothyroxine (1-thyroxine) is considered to be drug of choice. The thyroid preparations are either natural (i.e., desiccated thyroid and thyroglobulin) or synthetic (levothyroxine, fiothyronine, and fiotrix) in origin. The availability of sensitive and specific assays for total and free hormone levels as well as TSH... 

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