Dianhydrogalactitol (NSC-132313): Pharmacokinetics in Normal and Tumor-Bearing Rat Brain and Antitumor Activity Against Three Intracerebral Rodent Tumors 2

Abstract

Dianhydrogalactitol (DAG; NSC-132313), a hexitol epoxide, was used to treat intracerebral rodent tumors. DAG was most active against the murine ependymoblastoma [treated/controls (TIC)>440%], less active against murine glioma 26 (T/C≈112–150%), and least active against rat 9L gliosarcoma (T/C=100%). Application of a two-compartment open model for plasma disappearance of HC-DAG in rats gave a volume of distribution at steady state of approximately 872 ml, a clearance of approximately 9.4 ml/minute, and an elimination constant of 0.025/minute. Entry of ¹⁴C-DAG was more rapid into the 9L tumor than into the normal brain. When a two-compartment series model for brain and tumor entry was applied, the t1/2 (half-time) for compartmental equilibrium was approximately 22 and 105 minutes in the brain, and 4 and 56 minutes in the 9L tumor. The drug rapidly entered the brain and tumor intracellular compartments. Binding to RNA was linear with time, and the absolute amount of binding...