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Rabbit Brain Concentrations of Doxorubicin During Intraarterial Infusions

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Neuro-Oncology

Part of the book series: Developments in Oncology ((DION,volume 66))

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Abstract

This study was undertaken to evaluate hydrophilic antitumor agents administered in intraarterial (IA) infusions. Brain distributions of doxorubicin (Adriamycin, ADR) after IA infusions were determined in rabbit VX-2 brain tumor model. With right carotid infusions of ADR (8 rabbits), tumor center concentrations averaged 3.3 ± 1.42 μg/g (mean ± 1 SE), concentrations at least 100 times greater than in vitro inhibitory concentrations (IC50) of ADR for human gliomas. ADR concentrations in brain-around-tumor averaged 2.43 ± 0.81 μg/g, but were only 0.104 ± 0.019 μg/g in non-tumor-bearing hemisphere. In 15 rabbits with VX-2 brain tumors, carotid artery infusions of ADR increased mean survival times by 20.9 ± 8.3%. These findings are supported by animal study using IA infusions of ADR after hyperosmotic blood-brain barrier (BBB) disruption and study in brain tumor patients using IA infusions of ADR. These results show that significant amounts of relatively non-lipophilic drugs, with IA infusions, can penetrate brain tumor areas but still spare normal areas from toxic drug exposure.

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References

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Authors and Affiliations

  1. Department of Neurosurgery, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, 44195-5226, U.S.A.

    Samuel J. Hassenbusch M.D., Ph.D.

Authors
  1. Samuel J. Hassenbusch M.D., Ph.D.
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Editors and Affiliations

  1. University of Pavia, Pavia, Italy

    P. Paoletti (Professor of Neurosurgery), G. Butti (Assistant Professor of Neurosurgery) & S. Pezzotta (Associated Professor of Neurosurgery) (Professor of Neurosurgery),  (Assistant Professor of Neurosurgery) &  (Associated Professor of Neurosurgery)

  2. Department of Neurosurgery, University of Tokyo, Tokyo, Japan

    K. Takakura (Professor and Chairman) (Professor and Chairman)

  3. Division of Stroke and Trauma, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, U.S.A.

    M. D. Walker (Director) (Director)

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© 1991 Springer Science+Business Media Dordrecht

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Hassenbusch, S.J. (1991). Rabbit Brain Concentrations of Doxorubicin During Intraarterial Infusions. In: Paoletti, P., Takakura, K., Walker, M.D., Butti, G., Pezzotta, S. (eds) Neuro-Oncology. Developments in Oncology, vol 66. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3152-0_39

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  • DOI: https://doi.org/10.1007/978-94-011-3152-0_39

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5390-7

  • Online ISBN: 978-94-011-3152-0

  • eBook Packages: Springer Book Archive

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