The accumulation of topotecan in 9L glioma and in brain parenchyma with and without dexamethasone administration

The accumulation of the topoisomerase I inhibitor topotecan in brain tumor as well as in brain around tumor (BAT) and normal brain following an intrav enous 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 topotec an was examined. Tumor, BAT and brain tissue as well as whole blood were co llected at 1 h after an i.v. bolus of topotecan. Concentrations of total to potecan in tumor, BAT and brain were quantified with high-performance liqui d chromatography (HPLC) and compared with concentrations in plasma of total topotecan. In brain tumor tissue the mean total topotecan concentration wa s 96 +/- 33 ng/g which was 20-fold higher than the accumulation of topoteca n 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 i n either tissue. We conclude that high tissue concentrations of topotecan c an be reached in experimental brain tumors in rats. This observation may be useful in the design of clinical studies with topotecan.