Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Feb 2008
Pharmacokinetics of gemcitabine in tumor and non-tumor extracellular fluid of brain: an in vivo assessment in rats employing intracerebral microdialysis.
Gemcitabine is a pyrimidine nucleoside analogue anticancer agent that has shown promising anti-tumor activity in several experimental models of brain tumor. However, the pharmacokinetic behavior of gemcitabine in the central nervous system, especially in brain tumors is currently not well understood. In this study we evaluated the gemcitabine brain extracellular fluid (ECF) in normal rats and in ECF obtained from tumor- and tumor-free regions of glioma-bearing rats, to better understand the availability of the drug to brain and brain tumors. ⋯ Our findings suggest that the overall brain exposure to gemcitabine is likely to be low as evident from the relative brain distribution coefficient of <0.1. However, the exposure is likely to be considerably higher in the brain tumor relative to tumor-free regions of the brain. The higher drug levels in brain tumor compared to the non-tumor region may facilitate selectively higher cytotoxicity against brain tumor cells.