Disposition of new sulphur-containing 2-(chloroethyl)nitrosoureas in rats

N'-(2-Chloroethyl)-N-[2-(methylsulphinyl) ethyl] and N'-(2-chloroethyl)-N-[2-(methylsulphonyl) ethyl]-N and N'-nitrosoureas (CMSOEN1, CMSO2EN1, CMSOEN2 and CMSO2EN2) are new nitrosoureas derived from cysteamine. Two of them (CMSOEN2 and CMSO2EN2) have shown excellent efficacy against several murine tumours. The inactive agents (CMSOEN1 and CMSO2EN1) display low alkylating activity but high carbamoylating activity. In contrast, the active agents (CMSOEN2 and CMSO2EN2) are strong alkylating agents but relatively weak carbamoylators. The disposition of CMSOEN2 and CMSO2EN2 was studied in rat, using two differently labelled species of each compound, administered i.v. (60 mumol/kg). Plasma disappearance, tissue distribution (with the exception of the brain) and elimination of radioactivity are similar for the two compounds similarly labelled. In contrast, these parameters are strongly influenced by the label position used. Plasma disappearance of unchanged CMSOEN2 and CMSO2EN2 follows a first-order kinetic process with the same half-life for both compounds (30-31 min). More unchanged CMSO2EN2 is found in brain compared to its congener (55 nmol/g and 37 nmol/g respectively at five minutes). This is most likely the consequence of the higher lipophilic character of the former compound. The breakdown product 2-chloroethanol was identified in plasma.