Pharmacokinetics and Dose Range-Finding of 8-Chloroadenosine-3',5'-Cyclic Monophosphate (NSC-614491) in Beagle Dogs.

摘要

8-Chloroadenosine-3',5'-cyclic monophosphate, sodium salt (8-Cl-cAMP) was chosen as a potentially useful cancer chemotherapeutic agent by the Decision Network Committee of the Development Therapeutics Program (DTP), Division of Cancer Treatment of the National Cancer Institute (NCI) to undergo preclinical toxicology testing. 8-Cl-cAMP demonstrated a major regulatory effect on the growth of several human cancer cells including breast, colon, lung, and gastric carcinomas, fibrosarcomas, gliomas, and leukemias. In addition to inhibiting the cancer cells grown in culture, the compound inhibits the growth in athymic mice of human cancer xenographs of various cell types including breast, colon, and lung carcinomas. The objectives of the study were to determine the plasma elimination pharmacokinetics of 8-Cl-cAMP and to evaluate the toxicity resulting from a single intravenous dose in male and female dogs.