A preliminary Pharmacokinetic study of dianhydrogalactitol (NSC-132313) disposition in the dog.
The pharmacokinetics of dianhydrogalactitol (DAG), NSC-132313, were studied in the beagle dog at doses of 3 mg - kg-1 and 6 mg - kg-1. DAG concentrations in plasma were determined by a gas chromatographic method capable of specifically detecting the parent drug and differentiating between it and products of its degradation or metabolism. Plasma disappearance time curves were generated and shown to follow simple two-compartment model behavior after iv administration of DAG. Distribution and elimination of DAG appeared to be dose-independent in the limited dose range studied. After iv administration, the drug was rapidly distributed throughout extracellular fluids (volume of the central compartment = 462 ml - kg-1) and subsequently was rapidly cleared (total body clearance = 23.4 ml - min-1 - kg-1) and eliminated (t1/2, b = 26.2 min) from the animal. Experiments (in vitro) with the use of radiolabeled DAG indicated that the drug binds reversibly and irreversibly to red blood cells.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D002849:Chromatography, Gas; D004285:Dogs; D004912:Erythrocytes / Q000378:metabolism; D004988:Ethers, Cyclic / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D004376:Galactitol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D013402:Sugar Alcohols / Q000378:metabolism*
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D013402:Sugar Alcohols; D004376:Galactitol