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Disposition and Metabolism of 1-(2-Chloroethyl)-3-(2',3',4'-tri-O-acetyl, ribopyranosyl)-1-nitrosourea in Rats¹

Institut National de la Santé et de la Recherche Médicale, Unit 71, Boîte Postale 184, 63005 Clermont-Ferrand [D. G., M-F. M., J-C. M.], and Faculté de Médecine, Services de Biophysique et de Cancérologie, 28 Place Henri Dunant, 63001 Clermont-Ferrand [J. D., R. P.], France

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 present study deals with the disposition and the metabolism in rats of three ¹⁴C-labeled species of RPCNU. The chemical plasma half-life of the drug was less than 5 min. Within the first 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 of [ethyl-¹⁴C]RPCNU showed that thiodiacetic acid and its sulf-oxide were major metabolites 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.

¹ Supported by grants from Fédération Nationale des Centres de Lutte contre le Cancer and Délégation Générale à la Recherche Scientifique et Technique (No. 78-7 2653). Presented in part at the international symposium, "Nitrosoureas in Cancer Treatment," Montpellier, France, January 26 to 27, 1981.

² To whom requests for reprints should be addressed.

Received 4/28/80. Accepted 10/ 6/81.