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Preclinical pharmacokinetics and antitumor activity of imexon


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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  1. 1.

    Bicker U, Fuhse P: Carcinostatic action of 2-cyanaziridines against a sarcoma in rats. Exp Path Bd. 10:279–284, 1975

  2. 2.

    Bicker UF: Immunopharmacological properties of 2-cyanaziridine derivatives. In: Fenichal RS, Chirigos MA (eds) Immune Modulation Agents and Their Mechanisms. Marcel Dekker, New York, 1975, pp 447–473

  3. 3.

    Hersh EM, Gschwind CR, Taylor CW, Dorr RT, Taetle R, Salmon SE: Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cellsin vitro. J Natl Cancer Inst 84:1238–1244, 1992

  4. 4.

    Salmon SE, Hersh EM: Sensitivity of multiple myeloma to imexon in the human tumor cloning assay. J Natl Cancer Inst 86(3):228–230, 1994

  5. 5.

    Gibaldi M, Perrier D: Chapter 5: Apparent volume of distribution. In: Pharmacokinetics, Second Edition, Marcel Dekker, Inc., New York, 1982, pp 199–219

  6. 6.

    Gehan EA: A generalized Wilcoxon test for comparing arbitrarily singly-censored samples. Biometrika 52:203–209, 1965

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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).

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Key words

  • Imexon
  • pharmacokinetics
  • aziridines
  • leukemia