Metabolism of a new radioprotector; S-acetyl-N-glycyl cysteamine. I. Absorption, distribution and excretion metabolites in mice bearing EMT6 tumours.
1. The disposition of S-acetyl-N-glycyl cysteamine (I) labelled with 14C on the cysteamine group (label 1), the glycyl group (label 2) and the acetyl group (label 3) has been studied in mice bearing EMT6 tumours. 2. Label 1 was mainly excreted in urine (63.1% dose in 24 h). Label 2 elimination was both in urine (36.0% dose in 24 h) and in expired air as 14CO2 (12.1% dose in 24 h). Label 3 was essentially eliminated in expired air as 14CO2 (55.4% dose in 24 h). 3. Tissue distribution studies of label 1 and label 2 showed that concentrations in tissues were higher than blood concentration as early as 10 min after administration. Whichever label was used, only little radio-activity was found in EMT6 tumour and brain. 4. Analysis of the urinary elimination products showed the presence of unchanged I and of cystamine, N-acetylcystamine, N-acetyl-S-methyl cysteamine sulphoxide and taurine. I is a prodrug of cysteamine which is released after deacetylation and hydrolysis of the amide bond. A metabolic pathway is proposed for this new radioprotective agent.
Maurizis
J C
JC
INSERM U 71 Clermont-Ferrand, France.
Godeneche
D
D
Madelmont
J C
JC
Moreau
M F
MF
Oiry
J
J
Imbach
J L
JL
Veyre
A
A
D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005998:Glycine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D011837:Radiation-Protective Agents; D003543:Cysteamine; C058950:S-acetyl-N-glycylcysteamine; D005998:Glycine