Pharmacology and neurotoxicity of cis-diamminedichloroplatinum, bleomycin, 5-fluorouracil, and cyclophosphamide administration following osmotic blood-brain barrier modification

E. A. Neuwelt, P. A. Barnett, M. Glasberg, E. P. Frenkel

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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 chamotherapeutic agents are used in a conventional manner appears to be due to the presence of the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)5278-5285
Number of pages8
JournalCancer Research
Volume43
Issue number11
StatePublished - 1983

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Bleomycin
Blood-Brain Barrier
Fluorouracil
Cyclophosphamide
Cisplatin
Pharmacology
Physiological Effects of Drugs
Canidae
Rodentia
Brain
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pharmacology and neurotoxicity of cis-diamminedichloroplatinum, bleomycin, 5-fluorouracil, and cyclophosphamide administration following osmotic blood-brain barrier modification. / Neuwelt, E. A.; Barnett, P. A.; Glasberg, M.; Frenkel, E. P.

In: Cancer Research, Vol. 43, No. 11, 1983, p. 5278-5285.

Research output: Contribution to journalArticle

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