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Cyclophosphamide — ¹⁴C Metabolism in the Angora Rabbit¹

Institut National de la Recherche Agronomique, 78350 — Jouy-en-Josas, France

Abstract

Cyclophosphamide-¹⁴C (mustard group labeled) was administered orally to angora rabbits, and the long term metabolism of this substance was then studied. A balance experiment showed the following distribution of ¹⁴C: urine, 94%; feces, 2%. Urinary elimination was very quick in the first hours following administration, then stretched over a long period (T = 9 days). Tissue elimination was biphasic and followed a comparable process. Results were compared with those of a preceding work done with CPA-³²P, and led to the conclusions that tissue residues do not have alkylating activity, open-nucleus alkylating metabolites are present at the same time as phosphorated non-alkylating metabolites (loss of mustard group), and an enterohepatic cycle is involved in the metabolic process.

¹ Supported in part by Institut Technique Ovin et Caprin (Contract No. 65865) and Syndicat National Angora Qualite (Contract No. 65804).

² The authors thank R. G. Thebault, Jocelyne Malhautier and Josiane Woirhaye for technical assistance.