Brain, CSF, and tumor pharmacokinetics of alpha-difluoromethylornithine in rats and dogs.
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.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D004285:Dogs; D000518:Eflornithine; D007700:Kinetics; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D009952:Ornithine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009952:Ornithine; D000518:Eflornithine