Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration

G. Cavaletti, E. Cavalletti, N. Oggioni, C. Sottani, C. Minoia, M. D'Incalci, M. Zucchetti, P. Marmiroli, G. Tredici

Research output: Contribution to journalArticle

Abstract

The distribution of paclitaxel (Taxol®) within the central and peripheral nervous system after repeated administration of this antineoplastic agent is still largely unknown. In this study we determined for the first time paclitaxel tissue concentration in the brain, spinal cord, dorsal root ganglia (DRG) and sciatic nerve using an experimental paradigm in the rat which reproduces the features of paclitaxel peripheral neurotoxicity in humans. Pathological confirmation of the onset of paclitaxel-induced peripheral neurotoxicity was performed. In order to achieve reliable results even with low concentrations of paclitaxel, a newly reported analytical method (high-performance liquid chromatography with tandem mass spectrometry) was used. We demonstrated that paclitaxel has easy access to the DRG, where it accumulates, while the lowest concentrations of the drug were measured in the brain. The intermediate concentrations of paclitaxel observed in the sciatic nerve and spinal cord may be due to paclitaxel transport along the centrifugal and centripetal branches of the DRG neuron axons. (C) 2000 Intox Press, Inc.

Original languageEnglish
Pages (from-to)389-394
Number of pages6
JournalNeuroToxicology
Volume21
Issue number3
Publication statusPublished - 2000

Keywords

  • HPLC
  • Nervous System Distribution
  • Neurotoxicity
  • Paclitaxel
  • Tandem Mass Spectrometry

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

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    Cavaletti, G., Cavalletti, E., Oggioni, N., Sottani, C., Minoia, C., D'Incalci, M., Zucchetti, M., Marmiroli, P., & Tredici, G. (2000). Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. NeuroToxicology, 21(3), 389-394.