Prostatic atrophy in dogs after intravenous administration of a ureido-ethylimidazoline derivative (CGP15'720A).
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, serum-chemistry 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 serum-chemistry aberrations in the treated dogs. The most consistent histopathological finding was prostatic atrophy, which was detected in 5/12 dogs in this series.
Kanter
P M
PM
James T. Grace Jr., Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Bullard
G A
GA
Pavelic
Z P
ZP
D000135:Acid Phosphatase / Q000096:biosynthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000633:toxicity; D001284:Atrophy / Q000139:chemically induced; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010671:Phenylurea Compounds / Q000009:adverse effects* / Q000633:toxicity; D011467:Prostate / Q000187:drug effects / Q000473:pathology*
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; C033192:1-(2-(2-(4-pyridyl)-2-imidazoline-1-yl)ethyl)-3-(4-carboxyphenyl)urea; D000135:Acid Phosphatase