Abstract
Purpose: Comparison of the influence of two different brain tumors (C6 and CNS1 glioma) on methotrexate (MTX) disposition in plasma, brain, and tumor tissue extracellular fluid (ECF).
Methods: Serial collection of plasma samples and brain ECF dialysates after i.v. bolus administration of MTX (50 mg kg-1) for 4 h. Quantitation of MTX concentrations by HPLC-UV.
Results: Histological studies revealed a 3-fold higher number of blood vessels in CNS1 than in C6 tumor tissue. In vivo recoveries (reverse dialysis) were significantly different in tumor tissue (C6: 8.0 ± 3.8%; CNS1: 4.9 ± 2.5%), and in the contralateral hemisphere (C6: 6.0 ± 4.0%; CNS1: 3.9 ± 2.5%) between the two tumors. Area under the concentration–time curve (AUC) in plasma was 30% higher in CNS1 than in C6 due to a lower systemic clearance. Maximum MTX levels in brain tumor ECF were significantly higher in CNS1 than in C6, and decreased faster in CNS1 than in C6 tumor-bearing rats. Penetration in tumor ECF (AUCECF/AUCPlasma ratio) was similar in CNS1 and C6. MTX concentrations in contralateral hemisphere were significantly lower than in tumor tissue and dependent on tumor model.
Conclusion: C6 and CNS1 brain tumors have a distinct yet highly variable impact on MTX penetration in brain and brain tumor ECF.
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Dukic, S.F., Kaltenbach, M.L., Heurtaux, T. et al. Influence of C6 and CNS1 Brain Tumors on Methotrexate Pharmacokinetics in Plasma and Brain Tissue. J Neurooncol 67, 131–138 (2004). https://doi.org/10.1023/B:NEON.0000021820.12444.4c
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DOI: https://doi.org/10.1023/B:NEON.0000021820.12444.4c