The transport and reaction of cisplatin in the brain of the rat has been investigated with the intent of refining estimates of associated parameters. These parameters are needed to prospectively model various tumor treatment modalities for expected efficacy. A steady-state reaction-diffusion model was capable of representing the total platinum concentration profiles in the cerebellum following a continuous 7-day infusion of drug. The infusate cannula was treated as a point source and flow of drug into CSF was shown to be negligible. Reaction of cisplatin with the sulfur-containing moieties of cells was examined in detail. Saturation of binding sites, primarily composed of cysteine, methionine, and some histidine residues, was found to occur within 1 mm of the cannuula tip. Saturation was modeled approximately as the reaction of free cisplatin with the time-averaged unbound protein concentration. At distances far from the cannula, e.g. 4 mm, protein degradation products containing platinum begin to contribute to the total platinum profile but they were shown to account for only about 3% and no more than 20% of the total present. The best linear reaction rate of cisplatin with protein was found to be .005 .002 min(-1). Inclusion of convection effects near the cannula tip decreases this value, but by no more than 30%, while saturation effects tend to increase it by about 40%. The capillary permeability was found to equal 9.0x10(-7) cm/sec and be nearly unaffected by saturation.
