Pharmacology of intrathecal VP-16-213 in dogs

Niramol Savaraj, Lynn G. Feun, Katherine Lu, Kenneth Gray, C. Wang, Ti Li Loo

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

VP-16-213 is an anticancer drug that is active against a number of malignancies including small cell lung cancer, lymphoma, and leukemia which are often complicated by the development of leptomeningeal carcinomatosis. To investigate the potential usefulness of VP-16-213 for intrathecal administration, the pharmacology and toxicity of intrathecal VP-16-213 was determined. VP-16-213 at varying doses (0.01-1.0 mg · kg) was instilled intrathecally in dogs. Plasma, CSF, spinal cord, and brain tissue drug concentrations were determined by radiochemical and high performance liquid chromatography technique. Drug concentrations were strikingly higher in spinal cord tissue near the injection site compared to more distal cord sites. CSF concentration of VP-16-213 is 3-4 logs higher compared to concurrent plasma levels. Severe neurotoxicity occurred at the higher doses used. Due to limited diffusion and extremely low doses which could be used without life-threatening neurotoxicity, VP-16-213 does not appear to be a useful agent for intrathecal administration.

Original languageEnglish (US)
Pages (from-to)211-215
Number of pages5
JournalJournal of neuro-oncology
Volume13
Issue number3
DOIs
StatePublished - Jul 1 1992

Keywords

  • intrathecal
  • VP16

ASJC Scopus subject areas

  • Neuroscience(all)
  • Oncology
  • Clinical Neurology
  • Cancer Research

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