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  • Title: Pharmacokinetic study in a phase I trial with an alkylating agent, diacetyldianhydrogalactitol (DADAG).
    Author: Erdélyi-Tóth V, Kerpel-Fronius S, Kanyár B, Eckhardt S.
    Journal: Cancer Chemother Pharmacol; 1986; 16(3):257-63. PubMed ID: 3698167.
    Abstract:
    Diacetyldianhydrogalactitol (DADAG), a new alkylating hexitol derivative, was given in 30-min infusions for 5 consecutive days or as a single high-dose administration. The parent drug was eliminated in a biphasic manner, with a terminal half-life of 30-40 h. Dianhydrogalactitol (DAG), the main, pharmacologically active metabolite, appeared after a lag time of about 0.2-0.6 h. Its peak concentration was reached 1-2 h after termination of the infusion. The terminal elimination of DAG followed that of the parent compound. During the 5-day schedule slight accumulation was observed, and the plasma concentrations of both compounds approached the steady state. Over a dose range of 75-1050 mg/m2 the daily mean plasma concentrations of DADAG increased by only about 3-4 times. Dose-dependent expansions of the distribution volumes of the drug (Vc, V lambda, Vss) were observed. The behavior of DADAG and DAG in the body could be adequately described by a three-compartment open model. After equilibration the plasma levels of the parent compound and its metabolite were determined by the rate of return of DADAG from the peripheral compartment and its conversion to DAG.
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