DISPOSITION AND METABOLISM OF 1-(2-CHLOROETHYL)-3-(2',3',4'-TRI-O-ACETYL, RIBOPYRANOSYL)-1-NITROSOUREA IN RATS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (2) , 525-529
Abstract
The antineoplastic activity in animals of 1-(2-chloroethyl)-3-(2'',3'',4''-tri-O-acetyl, ribopyranosyl)-1-nitrosourea (RPCNU) has been widely demonstrated. The disposition and the metabolism in rats of 3 14C-labeled species of RPCNU were studied. The chemical plasma half-life of the drug was < 5 min. Within the 1st min after injection, most of the radioactivity derived from ethyl-14C groups was recovered as volatile products. Among these, 2-chloroethanol was identified as a main component. Analysis of labeled species in urine after administration [ethyl-14C]RPCNU showed that thiodiacetic acid and its sulfoxide were major metabolities of RPCNU (62% of the urinary radioactivity). Traces of N-acetylcarboxymethyl- and N-acetylhydroxyethylcysteine were also detected. The only labeled species concentrating in particular tissues was that carrying the chloroethyl moiety. Uptake to high levels of [ethyl-14C] RPCNU did occur in liver, kidney, pancreas, thymus and Harder''s gland.