Comparison of disposition behavior and de-coppering effect of triethylenetetramine in animal model for Wilson's disease (long-evans cinnamon rat) with normal Wistar rat
✍ Scribed by Ken Iseki; Michiya Kobayashi; Ayumi Ohba; Dr. Katsumi Miyazaki; Yu Li; Yuji Togashi; Noritoshi Takeichi
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 543 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The disposition behaviors and de-coppering effect of triethylenetetramine dihydrochloride (trientine), a selective chelating agent for copper and an 'orphan drug' for Wilson's disease, have been evaluated in an animal model, Long-Evans Cinnamon (LEC) rats, and normal rats (Wistar). In LEC rats, urinary excretion of trientine was remarkably lower than that of Wistar rats. The absorption rates from the jejunal loop and in vitro metabolism in the liver S9 fraction (supernatant of 9OOO X g) were approximately the same for both strains. The decline of urinary excretion of trientine in LEC rats is thought to be due mainly to the lowering of the functional activity of the kidney, because urinary excretion of creatinine and phenolsulfonphthalein were significantly lower in LEC rats than those in Wistar rats. Both acceleration of urinary excretion of copper and reduction of hepatic copper levels were observed with treatment of trientine in LEC rats aged 6 weeks. In LEC rats aged 13 weeks, however, no de-coppering effect from the liver was observed, though urinary excretion of copper was increased. These results suggest that trientine has a pharmacological effect in disease state, especially in the early stages of hepatitis.