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The anticancer drug vinorelbine (Navelbine) is currently formulated as a 5 microg mL(-1) elixir containing 10% ethanol. It has been demonstrated that the availability of the drug in human plasma has a major role in its in vivo antineoplastic action. This report presents a microdialysis study in rats to provide data characterising the pharmacokinetic behaviour of Navelbine. Also presented is a pharmacodynamic characterisation of the drug in the rat brain using microdialysis. Microdialysis probes for the determination of the drug in the brain dialysate were constructed using proprietary double-lumen designs. Following in vivo implantation in the interstitial fluid space of the brain, probes were perfused with artificial CSF. Intravenous injections of Navelbine were made, with samples of plasma and brain dialysate being taken at different times to define the pharmacokinetic behaviour of the drug. Vascular protein binding of the drug in the rat brain was also determined. The results were compared with data obtained for vinorelbine using the same methodology in human plasma (author’s unpublished data). The results for both the in vitro and the in vivo studies are presented and discussed. The results of the in vitro study show that the protein binding of vinorelbine in the rat brain is much greater than that in human plasma, in accordance with other findings that suggest a much lower protein binding in the brain of rats than in humans. The results of the in vivo study show that: (1) the drug rapidly enters the rat brain dialysate; (2) the half-life of the drug in rat brain dialysate is approximately the same as in human plasma; (3) the drug was totally eliminated from the rat brain within 24 h; (4) drug concentrations were much greater in the rat brain than in the plasma; and (5) therapeutic concentrations of the drug can be achieved in the brain with the concentrations in plasma being approximately twice as high. Microdialysis appears to be a suitable methodology to determine the pharmacokinetic behaviour of drugs in the brain of humans and of other animals.
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