Rabbit Brain Concentrations of Doxorubicin During Intraarterial Infusions
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.
KeywordsBrain Tumor Patient Glioma Cell Sensitivity Carotid Artery Flow Microculture Tetrazolium Assay Brain Tumor Chemotherapy
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