The effect of vitamin b6 on the neurotoxicity and pharmacology of desmethylmisonidazole and misonidazole: Clinical and laboratory studies

C. Norman Coleman, V. Kate Hirst, Dennis M. Brown, Joanne Halsey

Research output: Contribution to journalArticlepeer-review

Abstract

The clinical usefulness of misonidazole (MISO) and desmethylmisonidazole (DMM) is severely limited by neurotoxicity. Based on theoretical considerations and on laboratory data suggesting that pyridoxine (PN) decreased MISO toxicity in mice,10 we attempted to ameliorate the clinical neuropathy of DMM using oral PN. Pharmacokinetic analysis suggested interaction of PN and DMM but no protection against neuropathy was observed. Serial experiments with C3H and BALB/c mice were done using various forms of vitamin B6 (PN, pyridoxal, pyridoxal phosphate) administered orally and i.p. and the nonspecific adsorbing agent activated charcoal. No consistent protection was observed. A slower rate of drug delivery (dose/day) allowed a larger cumulative dose of MISO to be given, a result paradoxical to that seen in the clinic. Dexamethasone did not after MISO toxicity in mice, contrary to the clinical findings. We conclude that vitamin B6 is not useful in preventing clinical neurotoxicity of MISO or DMM. Furthermore, this mouse model of neurotoxicity assessment has produced results inconsistent with those seen clinically.

Original languageEnglish (US)
Pages (from-to)1381-1386
Number of pages6
JournalInternational journal of radiation oncology, biology, physics
Volume10
Issue number8
DOIs
StatePublished - Aug 1984

Keywords

  • 2-nitroimidazoles
  • Desmethylmisonidazole
  • Misonidazole
  • Neuropathy
  • Vitamin B

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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