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Cancer Chemotherapy and Pharmacology

, Volume 31, Issue 2, pp 127–130 | Cite as

Intrathecal 5-fluorouracil in the rhesus monkey

  • Stacey L. Berg
  • Frank M. Balis
  • Cynthia L. McCully
  • George A. Parker
  • Robert F. Murphy
  • David G. Poplack
Original Articles 5-Fluorouracil, Intrathecal Therapy, Pharmacokinetics

Summary

Because meningeal spread of both leukemia and solid tumors remains a difficult therapeutic problem, there is a compelling need to develop new agents for intrathecal administration. 5-Fluorouracil (5FU), an active anticancer agent, penetrates into the central nervous system to some degree following intravenous dosing. Significant systemic toxicity, however, is associated with this route of administration. Therefore, the pharmacokinetic behavior of 5FU following its intrathecal administration was studied in a rhesus monkey model. After a 10-mg intraventricular dose, the disappearance of the drug from ventricular cerebrospinal fluid was monoexponential, the half-life being 51 min; the area under the concentration-time curve (AUC) being greater than 18mm h−1; and the peak ventricular 5FU concentrations ranging between 10 and 15mm. After a 1-mg intralumbar dose, the AUC was 1235 μm h−1. No toxicity was observed following intraventricular administration of 5FU. After intralumbar administration of either a 10-mg or a 1-mg dose, however, local toxicity was observed in the lumbar spinal cord. These findings suggest that intrathecal administration of 5FU is not presently a feasible means of achieving cytotoxic cerebrospinal fluid concentrations.

Keywords

Rhesus Monkey Monkey Model Fluid Concentration Lumbar Spinal Cord Intrathecal Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Stacey L. Berg
    • 1
  • Frank M. Balis
    • 1
  • Cynthia L. McCully
    • 1
  • George A. Parker
    • 1
  • Robert F. Murphy
    • 1
  • David G. Poplack
    • 1
  1. 1.Pediatric BranchNational Cancer InstituteBethesdaUSA

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