Preclinical pharmacokinetics and antitumor activity of imexon

Robert T Dorr, James D. Liddil, Mary Kay Klein, Evan M Hersh

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 lines in 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 obtained in vivo and that imexon is active in lymphoproliferative tumors.

Original languageEnglish (US)
Pages (from-to)113-116
Number of pages4
JournalInvestigational New Drugs
Volume13
Issue number2
DOIs
StatePublished - Jun 1995

Fingerprint

Pharmacokinetics
Pharmaceutical Preparations
Dogs
Leukemia L1210
Neoplasms
Multiple Myeloma
Human Activities
Mast Cells
Melanoma
Animal Models
High Pressure Liquid Chromatography
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
Lymphocytes
Cell Line

Keywords

  • aziridines
  • Imexon
  • leukemia
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Preclinical pharmacokinetics and antitumor activity of imexon. / Dorr, Robert T; Liddil, James D.; Klein, Mary Kay; Hersh, Evan M.

In: Investigational New Drugs, Vol. 13, No. 2, 06.1995, p. 113-116.

Research output: Contribution to journalArticle

Dorr, Robert T ; Liddil, James D. ; Klein, Mary Kay ; Hersh, Evan M. / Preclinical pharmacokinetics and antitumor activity of imexon. In: Investigational New Drugs. 1995 ; Vol. 13, No. 2. pp. 113-116.
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