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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

3'-isopropyl-3,5-diiodo-L-thyronine: a potent synthetic thyromimetic thyronine analog. Studies of its kinetics and biological potency in man and rats and its toxicology.

In order to compare phenolic and tyrosyl ring monodeiodination, we investigated 3'-isopropyl-3,5-diiodo-L-thyronine (DIIP), a potent thyronine analog which can only be monodeiodinated on the tyrosyl ring. A specific RIA was developed. The in vivo metabolism and biological potency of DIIP and T3 were compared. DIIP and T3 kinetic studies were performed in vivo using 40 male SIVZ rats who received 5 micrograms DIIP and 0.5 microCi 131I-T3. Blood samples were obtained for up to 15 h. The MCR of DIIP was 2.8 ml/h/100 g BW and the volume of distribution was 27 ml/100 g BW, corresponding values for T3 being 34 ml/h/100 g BW and 175 ml/100 g BW. Subacute toxicology studies in rats showed that DIIP was not more toxic than T3. On the basis of these results, experiments were performed in man. Five male subjects received 40 micrograms DIIP p.o. and blood samples were collected over 17 days. The MCR was 54 ml/kg . day, the volume of distribution 188 ml/kg and the fractional disappearance rate 0.0119/h. When given to an hypothyroid patient, 16-20 micrograms DIIP daily was sufficient to restore clinical and biochemical euthyroidism. These studies demonstrate that a decreased MCR can be accompanied by increased biological activity. It is suggested that the limited monodeiodination of DIIP is one of the factors explaining the differences observed in the potency and metabolism of DIIP and T3.[1]


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