Summary
We have determined the pharmacokinetic parameters for diffusion of α-[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.
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Levin, V.A., Csejtey, J. & Byrd, D.J. Brain, CSF, and tumor pharmacokinetics of α-difluoromethylornithine in rats and dogs. Cancer Chemother. Pharmacol. 10, 196–199 (1983). https://doi.org/10.1007/BF00255762
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DOI: https://doi.org/10.1007/BF00255762