Dose Range-Finding of Cyclodisone (NSC-348948) in Male Mice (Up-Down Bioassay)

摘要

Cyclodisone (NSC-348948; Cyclic SoSo) is an alkylating agent currently undergoing preclinical development at the National Cancer Institute (NCI). Liao and Merriman and Malspeis and Staubus have tested cyclodisone in mice and dogs. These studies were conducted using solutions of cyclodisone in DMSO which were administered by oral gavage and intravenous/intraperitoneal injection. After reviewing data from these studies, the NCI decided to develop a different formulation of the drug. In the present study, cyclodisone was dissolved in 0.3N NaOH and then these solutions were diluted to final volume with deionized water and administered orally (gavage) to CD2F1 mice. The maximum tolerated dose of cyclodisone in the CD2F1 mice in the study was between 380 and 437 mg/kg. Cyclodisone was less toxic when administered in a NaOH solution than had previously been reported for cyclodisone in a DMSO solution.