Metabolism of a New Radioprotector; S-Acetyl-N-Glycyl Cysteamine. I. Absorption, Distribution and Excretion Metabolites in Mice Bearing Emt6 Tumours

Abstract

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 24h) 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 10min 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.