Lack of stereoselectivity in the pharmacokinetics and metabolism of the radiosensitizer Ro 03-8799 in man

Cancer Chemother Pharmacol. 1991;28(2):118-22. doi: 10.1007/BF00689700.

Abstract

During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(-)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The pharmacokinetic data were compared with those for the racemic mixture in the same individuals. The results revealed no major differences in the plasma pharmacokinetics, urinary clearance or N-oxidation of the individual enantiomers as compared with the racemic mixture. A similar lack of stereoselectivity with respect to the acute dose-limiting CNS toxicity syndrome suggests that this may not involve a specific CNS receptor interaction.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Aged
  • Carcinoma, Squamous Cell / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Nitroimidazoles / blood
  • Nitroimidazoles / metabolism
  • Nitroimidazoles / pharmacokinetics*
  • Nitroimidazoles / urine
  • Radiation-Sensitizing Agents / metabolism
  • Radiation-Sensitizing Agents / pharmacokinetics*
  • Stereoisomerism

Substances

  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • pimonidazole