The vascular compartment hampers accurate determination of teniposide penetration into brain tumor tissue |
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Authors: | Olaf van Tellingen Willem Boogerd Willem J Nooijen Jos H Beijnen |
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Institution: | (1) Department of Clinical Chemistry, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, NL;(2) Department of Neuro-oncology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, NL;(3) Department of Pharmacy, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, NL |
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Abstract: | After a pre-operative 1-h i.v infusion of 150 mg/m2 of teniposide (Vumon; VM26), the drug levels were determined in resected brain tumor specimens from three patients with malignant
glioma and from three patients with brain metastases. Tissue dissections were performed within 0–2.5 h after drug administration
in three patients and after 24 h in the other three patients. Teniposide was quantified by high-performance liquid chromatography
and the levels of albumin in the resected tissue samples were quantified by radial immunodiffusion. In addition, albumin levels
were quantified in normal brain tissue, in malignant glioma and in metastatic brain tumor tissue obtained post mortem from
deceased patients. The albumin levels indicated that a substantial fraction (range: 0.16–0.50) of the resected brain tumor
specimens consisted of blood. As the plasma concentration of teniposide during the first hours after infusion is high, the
major part of the drug measured in the tumor specimens collected within 2.5 h after drug administration originated from the
blood compartment. At 24 h after drug administration, when the plasma level of teniposide had declined to approximately 0.20
μg/ml, we could discern a real tissue uptake of teniposide ranging from 0.15–0.27 μg/g wet tissue weight in the resected tumor.
Although the number of patients in this study is small, this work clearly illustrates that an accurate determination of the
tissue concentration of teniposide is hindered by the high concurrent plasma levels. It is therefore essential that future
tissue distribution studies also include a suitable procedure that establishes the contribution of drug originating from the
blood compartment.
Received: 4 November 1996 / Accepted: 15 February 1997 |
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Keywords: | Teniposide Brain Metastasis Malignant glioma |
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