Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue

Int J Radiat Biol. 1992 Aug;62(2):221-7. doi: 10.1080/09553009214552041.

Abstract

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Hypoxia* / drug effects
  • Cell Hypoxia* / radiation effects
  • Etanidazole
  • Female
  • Half-Life
  • Mice
  • Mice, Inbred C3H
  • Nitroimidazoles / metabolism
  • Nitroimidazoles / pharmacokinetics*
  • Peripheral Nerves / metabolism*
  • Radiation-Sensitizing Agents / pharmacokinetics*

Substances

  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • KU 2285
  • Etanidazole