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The Accumulation of Topotecan in 9L Glioma and in Brain Parenchyma with and without Dexamethasone Administration

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Abstract

The accumulation of the topoisomerase I inhibitor topotecan in brain tumor as well as in brain around tumor (BAT) and normal brain following an intravenous bolus of topotecan of 0.5 mg/kg was investigated in rats bearing a 9L glioma. Also the influence of dexamethasone (Dex) on the uptake of topotecan was examined. Tumor, BAT and brain tissue as well as whole blood were collected at 1 h after an i.v. bolus of topotecan. Concentrations of total topotecan in tumor, BAT and brain were quantified with high-performance liquid chromatography (HPLC) and compared with concentrations in plasma of total topotecan. In brain tumor tissue the mean total topotecan concentration was 96±33 ng/g which was 20-fold higher than the accumulation of topotecan in normal brain tissue. In BAT intermediate concentrations of 13±4.9 ng/g were reached. Mean total topotecan concentration in plasma was 100±25 ng/ml. We did not find an influence of Dex on the uptake of topotecan in either tissue. We conclude that high tissue concentrations of topotecan can be reached in experimental brain tumors in rats. This observation may be useful in the design of clinical studies with topotecan.

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Authors and Affiliations

  1. Departments of Neuro-oncology, The Netherlands

    C.S.M. Straathof, M.J. van den Bent & Ch.J. Vecht

  2. Neurology and Laboratory of Experimental Chemotherapy and Pharmacy, Dr Daniel den Hoed Cancer Center and University Hospital Rotterdam, Rotterdam, The Netherlands

    C.S.M. Straathof

  3. Department of Medical Oncology, Dr Daniel den Hoed Cancer Center and University Hospital Rotterdam, Rotterdam, The Netherlands

    W.J. Loos & J.H.M. Schellens

Authors
  1. C.S.M. Straathof
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  2. M.J. van den Bent
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  3. W.J. Loos
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  4. Ch.J. Vecht
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  5. J.H.M. Schellens
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Straathof, C., van den Bent, M., Loos, W. et al. The Accumulation of Topotecan in 9L Glioma and in Brain Parenchyma with and without Dexamethasone Administration. J Neurooncol 42, 117–122 (1999). https://doi.org/10.1023/A:1006166716683

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  • DOI: https://doi.org/10.1023/A:1006166716683

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