Preclinical Pharmacokinetics and Toxicity Studies in CD2F1 Mice with 5-Azacytosine Arabinoside (NSC-281272). Volume 1

摘要

A single 200-mg intraperitoneal (IP) dose of 5-Azacytosine arabinoside (ARC-AC) (NSC-281272) has a similar bioavailability when compared to that of a single intravenous (IV) dose; the fraction absorbed by the IP dose was approximately 75% that of the IV dose. Multiple IP injections (up to 8) of 400- and 500-mg/kg and continuous administration (3 or more days) of 180 mg/kg/day were lethal. Clinical signs of neurotoxicity and nematopoietic injury were observed in treated mice when compared to those of the control. Macroscopic and/or microscopic pathologic lesions were characteristic of immunologic, hepatic, gastrointestinal, and testicular injury.