Limited cerebrospinal fluid penetration of docetaxel

Albert J. Ten Tije, Walter J. Loos, Ming Zhao, Sharyn D. Baker, Roelien H. Enting, Hans Van Der Meulen, Jaap Verweij, Alex Sparreboom

Research output: Contribution to journalArticlepeer-review

Abstract

Our purpose was to investigate the cerebrospinal fluid (CSF) penetration of docetaxel in cancer patients. Docetaxel was administered as a 1-h infusion at a dose of 75 mg/m2 to two patients with metastatic breast cancer and leptomeningeal carcinomatosis. CSF samples were obtained using a lumbar puncture up to a 72-h time period. Total and unbound docetaxel concentrations in plasma and CSF were determined by liquid chromatography (lower limit of quantitation: 0.5 nM for plasma and 0.050 nM for CSF) and equilibrium dialysis, respectively. The pharmacokinetics of docetaxel in plasma are in line with data of previous studies. The concentrations of docetaxel in CSF did not follow the general pattern in plasma, with relatively stable concentrations over the 72-h time period. The fraction of unbound docetaxel in plasma ranged from 6 to 13%, while that in CSF ranged from 67 to 103%. For total and unbound docetaxel, the CSF to plasma concentration ratio progressively increased in 72 h from 0.01 to 0.6% and from 0.1 to 9%, respectively. These data suggest that measurement of unbound docetaxel is required to accurately assess the extent of drug penetration into CSF and that the drug can produce distribution to CSF at levels associated with significant antitumor activity in experimental models.

Original languageEnglish (US)
Pages (from-to)715-718
Number of pages4
JournalAnti-cancer drugs
Volume15
Issue number7
DOIs
StatePublished - Aug 1 2004

Keywords

  • Cerebrospinal fluid
  • Docetaxel
  • Pharmacokinetics
  • Protein binding

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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