PMID: 9430094Jan 16, 1998Paper

Repeated dose toxicity studies of taltirelin tetrahydrate (TA-0910) with oral administration to dogs

The Journal of Toxicological Sciences
T InuiS Kudow

Abstract

Taltirelin tetrahydrate (TA-0910), novel thyrotropin-releasing hormone (TRH) analogue, was orally administered to dogs as dose levels 0.5, 5, and 50 mg/kg for 13 weeks and 0.15, 1.5 and 15 mg/kg for 52 weeks. Blood concentrations of test substance measured in 52-week study revealed that absorption of TA-0910 was with dose-dependent manner and not changed through the treatment period. These toxicokinetics suggested that there were no alterations on metabolism of TA-0910 with repeated treatment. The animals receiving 5 or 50 mg/kg showed decrease in body weight or suppression of body weight gain, and decrease in food intake (13-week study). As an abnormality in general conditions, vomiting and salivation (5 mg/kg or more, both in 13- and 52-week studies), increase in behavior as water intake (5 mg/kg or more, 13-week study), and hyperlocomotion (50 mg/kg) were observed. Elevating GPT values were noted temporally in the animals treated with 5 mg/kg or more (both in 13- and 52-week studies) without abnormal findings in histopathology. The thyroid weights were increased in treated animals receiving 5 or 50 mg/kg in 13-week study, but no histopathological changes were noted. Electron microscopy revealed dilatation of granular endopla...Continue Reading

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