Brain, CSF, and tumor pharmacokinetics of alpha-difluoromethylornithine in rats and dogs

Cancer Chemother Pharmacol. 1983;10(3):196-9. doi: 10.1007/BF00255762.

Abstract

We have determined the pharmacokinetic parameters for diffusion of alpha-[5-14C]-difluoromethylornithine (DFMO) from blood to brain, blood to cerebrospinal fluid (CSF), 9L rat brain tumor to adjacent brain, and blood to the subcutaneously-implanted 9L tumor in rats, and within the CSF of beagle dogs. DFMO diffusion across the blood-brain and blood-CSF barriers is quite restricted in both rats and dogs, but diffusion across the defective capillary system of both subcutaneous and intracerebral 9L tumors in rats is not. Under steady-state plasma conditions in rats, uptake of DFMO by the intracerebral 9L tumor and diffusion from tumor 5-6 mm into adjacent brain is not restricted; tissue/plasma ratios were approximately 1. Therapeutic efficacy will therefore not be limited by transport of DFMO into tumor or to the extracellular environment of tumor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Brain / metabolism*
  • Brain Neoplasms / metabolism*
  • Cerebrospinal Fluid / metabolism*
  • Dogs
  • Eflornithine
  • Kinetics
  • Neoplasm Transplantation
  • Neoplasms, Experimental
  • Ornithine / analogs & derivatives*
  • Ornithine / metabolism
  • Rats
  • Rats, Inbred F344
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Ornithine
  • Eflornithine