Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification

Edward Neuwelt, M. Pagel, P. Barnett, M. Glassberg, E. P. Frenkel

Research output: Contribution to journalArticle

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Abstract

The effect of reversible blood-brain barrier modification on the delivery of Adriamycin to the brain was studied in a rodent and canine model. Pharmacokinetic and physiological studies were done in these animals after a wide range of doses of Adriamycin (0.1 to 1.0 mg/kg) were administered into the carotid artery following osmotic barrier modification with mannitol. In the absence of barrier modification, no immunoreactive Adriamycin was detected in the cerebrum; whereas, following barrier modification, up to 4.5 μg of drug and/or metabolites per g of brain were found. Optimum tissue levels of Adriamycin and metabolites were achieved following barrier modification when the drug was administered by either bolus or slow continuous (15-min) infusion. Immunoreactive drug was identified in brain for up to 6 hr after administration. Significant functional neurotoxicity occurred at all dose levels, even at 0.1 mg/kg, a level at which Adriamycin concentration in the brain was below the level of detectability. Neuropathological examination revealed the presence of necrosis and hemorrhagic infarcts. Thus, these pharmacological and toxicity studies suggest that Adriamycin (or its metabolites) may produce significant clinical neurotoxicity when even small amounts penetrate the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)4466-4470
Number of pages5
JournalCancer Research
Volume41
Issue number11 I
StatePublished - 1981
Externally publishedYes

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Blood-Brain Barrier
Doxorubicin
Pharmacology
Brain
Pharmaceutical Preparations
Cerebrum
Mannitol
Carotid Arteries
Canidae
Rodentia
Necrosis
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification. / Neuwelt, Edward; Pagel, M.; Barnett, P.; Glassberg, M.; Frenkel, E. P.

In: Cancer Research, Vol. 41, No. 11 I, 1981, p. 4466-4470.

Research output: Contribution to journalArticle

Neuwelt, E, Pagel, M, Barnett, P, Glassberg, M & Frenkel, EP 1981, 'Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification', Cancer Research, vol. 41, no. 11 I, pp. 4466-4470.
Neuwelt, Edward ; Pagel, M. ; Barnett, P. ; Glassberg, M. ; Frenkel, E. P. / Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification. In: Cancer Research. 1981 ; Vol. 41, No. 11 I. pp. 4466-4470.
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