Chemical formula: C₁₄H₉I₃O₄ Molecular mass: 621.932 g/mol PubChem compound: 5803
Tiratricol (3,3',5-triiodothyroacetic acid) is a naturally circulating metabolite of active thyroid hormone (T3) with a high degree of structural similarity and follows the same downward degradation pathway (deiodination and conjugation) and elimination via bile and urine. Tiratricol is biologically active, binds with high affinity to the thyroid hormone receptors TRα and TRβ and exerts similar biological effects to T3, although with different tissue specificity. Tiratricol has been demonstrated to be able to enter MCT8 dependent cells without a functioning MCT8 transporter unlike T3 and T4. Tiratricol can thereby replace T3 in MCT8 dependent tissues and restore normal thyroid hormone activity across tissues.
The absorption of tiratricol following oral dosing is rapid with a median tmax of 0.5 hours following doses between 175 and 1 050 micrograms in fasted healthy volunteers.
The in vitro plasma protein binding of tiratricol is high, with protein binding of >99% in human plasma. The bioavailability of tiratricol (F) was 67 ± 6% suggesting tiratricol is well absorbed from the gastrointestinal (GI) tract.
Tiratricol is a naturally circulating metabolite of active T3 with a high degree of structural similarity and follows the same metabolic pathway. The major human metabolic pathway of tiratricol is by stepwise deiodination, sulfation and glucuronidation mainly in the liver, similar to T3.
Following Cmax, serum concentrations declined in a generally biphasic manner and remained quantifiable until between 3 and 48 hours post dose. The geometric mean t½ was between 13.3–14.0 hours for the 350 microgram and 1 050 microgram doses, respectively. Tiratricol is eliminated through bile and urine.
Cmax following treatment with the 175 microgram, 350 microgram, and 1 050 microgram doses (about 2 to 13.5 micrograms/kg bodyweight) increased proportionally with dose, whereas the area under the curve (AUC) increased in a slightly greater than proportional manner with increasing dose.
In the clinical trial studying the effect of tiratricol in patients with MCT8 deficiency, the dose was individually titrated based on T3 levels.
No conventional studies of carcinogenic potential have been conducted with tiratricol. Tiratricol was devoid of mutagenic activity when tested in the Ames Salmonella assay and showed no increase in chromosomal aberrations when tested in vitro and in vivo.
Embryofetal development studies showed embryolethality in rabbits and embryolethality and structural myocardial damage in rats. On a mg/body surface area (BSA) dose comparison, the no- observed-adverse-effect-levels (NOAELs) in the rat and rabbit studies were slightly lower and slightly higher, respectively, than the highest clinical dose in adult patients.
No effects on mating ability or fertility were observed in a study in male and female rats administered high and otherwise toxic doses of tiratricol.
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