Pharmacokinetic studies in dogs were performed with a series of three 2,2-dimethylaziridine antineoplastic agents. These alkylating agents were relatively unstable in all aqueous media, with half-lives of 9-15 min in whole canine blood. This finding indicates that the aziridine compounds are capable of undergoing destruction in all biological tissues. A pharmacokinetic analysis of the plasma concentration uersus time data was performed using a two-compartment open model, which includes drug elimination from both compartments. The three aziridine compounds showed similar pharmacokinetic behavior with respect to their loss from plasma, but they exhibited differences in their in uiuo release of a potent alkylating intermediate (2,2-dimethylaziridine) and a second product, which was a strong inhibitor of pseudocholinesterase.
Keyphrases 2,2-Dimethylaziridines-reactions in biological systems, comparative pharmacokinetics in dogs 0 Aziridines-2,2-dimethylaziridine-type alkylating agents, reactions in biological systems, comparative pharmacokinetics in dogs 0 Antineoplastic agents-reactions of 2,2-dimethylaziridine-type alkylating agents in biological systems, comparative pharmacokinetics in dogs 0 Pharmacokinetics-2,2-dimethylaziridine-type alkylating agents in biological systems, dogs ~~