Abstract
Direct comparisons of theoretical modeling with actual drug delivery can lead to improved brain tumor therapy. In this study, normal and brain tumor-bearing rabbits received infusions of BCNU, or carmustine (1,3-bis [2-chlorethyl]-1-nitrosourea), with ethanol or hyperoxygenated perfluorocarbons as BCNU diluent. When ethanol was used as a diluent, right (infused) hemisphere:left (noninfused) hemisphere ratios of BCNU concentrations in both rabbit groups were markedly lower than had been predicted with theoretical pharmacokinetic modeling. When perfluorocarbons were used as a diluent, ratios of BCNU were significantly improved. These laboratory studies were directly translated into a two-phase protocol for human brain tumor patients. This combined research program demonstrates the successful integration of laboratory and clinical programs.
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