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Preclinical pharmacokinetics and antitumor activity of imexon

Summary

Imexon is an aziridine compound originally studied for immune-enhancing effects on lymphocytes. The drug was well-tolerated in humans and was shown to be active in a variety of animal tumor models. Recently, imexon has demonstrated antitumor activity in human multiple myeloma cell linesin vitro. The pharmacokinetics of the compound using a normal phase HPLC assay were studied in normal mice and in dogs with mast cell tumors. Doses of 100 mg/kg given intraperitoneally produced peak plasma levels over 100 (μml in mice and the drug was rapidly eliminated with half lives of 8 minutes (α phase) and 29 minutes (β phase). Only 20% of an oral imexon dose was absorbed in the mouse. In dogs, the α and β phase half lives ranged from 18–26 minutes and 91–110 minutes, respectively. Peak levels over 100 μg/ml were obtained following intravenous doses of 12.5 mg/kg and 25 mg/kg. Imexon was active in mice bearing either P-388 or L-1210 leukemia, but not in mice with B-16 melanoma. These results suggest that cytotoxic drug concentrations can be obtainedin vivo and that imexon is active in lymphoproliferative tumors.

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Correspondence to Robert T. Dorr.

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Dorr, R.T., Liddil, J.D., Klein, M.K. et al. Preclinical pharmacokinetics and antitumor activity of imexon. Invest New Drugs 13, 113–116 (1995). https://doi.org/10.1007/BF00872858

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Key words

  • Imexon
  • pharmacokinetics
  • aziridines
  • leukemia