Abstract:
:cis-Platinum, bleomycin, 5-fluorouracil, and cyclophosphamide were administered to rodent and canine models of osmotic blood-brain barrier modification to evaluate the relationship between tissue drug concentration in brain and the physiological and neuropathological effects of the drug. The toxicity studies were carried out in the canine, and the pharmacological studies were carried out in the rodent. Even without the osmotic procedure, intracarotid cis-platinum, in contrast to the other drugs, produced modification of the blood-brain barrier with resultant severe neurotoxicity. Osmotic blood-brain barrier modification was used to increase delivery of bleomycin and 5-fluorouracil to the ipsilateral brain region, but the increased delivery was associated with evident neurotoxicity. Cyclophosphamide administration in association with osmotic blood-brain barrier opening did not cause significant neural toxicity. These studies indicate that some chemotherapeutic agents given in association with osmotic blood-brain barrier opening can result in neurotoxicity. The corollary of the known limited neurotoxicity when these chemotherapeutic agents are used in a conventional manner appears to be due to the presence of the blood-brain barrier.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Neuwelt EA,Barnett PA,Glasberg M,Frenkel EPsubject
Has Abstractpub_date
1983-11-01 00:00:00pages
5278-85issue
11eissn
0008-5472issn
1538-7445journal_volume
43pub_type
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