Metabolism of administered triethylene tetramine dihydrochloride in humans.
Triethylene tetramine dihydrochloride (trien 2HCl) has been used for the treatment of Wilson's disease, which is characterized by the accumulation of copper in various organs. We previously developed an HPLC system for analyzing trien, and found a trien metabolite in the urine when trien was orally given to humans. In this study, the metabolite was identified as 1-N-acetyltriethylene tetramine (acetyltrien) by FAB-MS and 1H-NMR spectroscopy. Trien and acetyltrien were capable of combining with copper, iron and zinc. However, the chelating activity of acetyltrien was significantly lower than that of trien. When trien was given to healthy adults, the amount of trien excreted in the urine was about 1% of the administered trien, whereas that of acetyltrien was about 8%. Most of the trien was excreted within the first 6 hours after the administration, while acetyltrien was excreted for over 26 hours. The urinary copper, iron and zinc levels all increased in parallel with the trien excretion.
Kodama
H
H
Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan. hkodama@med.teikyo-u.ac.jp
Murata
Y
Y
Iitsuka
T
T
Abe
T
T
D000284:Administration, Oral; D000328:Adult; D002614:Chelating Agents / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism / Q000652:urine; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014266:Trientine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D015032:Zinc / Q000378:metabolism / Q000652:urine
D002614:Chelating Agents; D003300:Copper; D007501:Iron; D015032:Zinc; D014266:Trientine