Prostatic atrophy in dogs after intravenous administration of a ureido-ethylimidazoline derivative (CGP15′720A)

Summary

1-{2-[4-Pridyl)-2-imidazoline-1-yl]-ethyl≃3-4-carboxyphenyl) urea (CGP15′720A) is an experimental antineoplastic agent with marked activity against carcinogen-induced lung tumors in Syrian hamsters and human lung tumor xenografts in nude mice. A preclinical toxicity study of this agent was carried out in mice and dogs which demonstrated the relatively nontoxic nature of the agent. In mice, single intraperitoneal dosage of 12 g/m² did not produce lethality; however, lethality (30% of treated mice) was seen during treatment with 6 g/m² daily for 5 days. No hematological, serumchemistry or histopathological changes were detected in mice after single or five consecutive treatments with 12 g/ m². Dogs were treated with doses ranging from 5 g/m² to 80 g/m², with deaths occurring in a non-dose-related fashion after 10, 20, and 40 g/m². Acute neurological toxicity after infusion was the dose-limiting toxicity in dogs. There were no consistent hematological or serumchemistry aberrations in the treated dogs. The most consistent histopathological finding was prostatic atrophy, which was detected in 5/12 dogs in this series.