In competition, the radical centres react with each other in recombination reactions that can either restitute the undamaged molecule or transform the free radicals into permanent molecular damage. The interactions between radicals are dominated by stereochemical factors and chemical reactivity. This last factor can be investigated in solutions of model compounds, and we have commenced a study of radical-radical reactions of DNA constituents. In the past year the re-birth in molecular studies has necessitated the commissioning of a further hplc system and the addition of a dedicated ion chromatograph. These have been used in several of the projects described above, and in other studies throughout the Laboratory.
Higher doses result in drug accumulation and significant toxicity.
We now wish to minimise variability in the rate of uptake of nicotinamide, especially the very slow absorption seen in some patients. Faster, more reproducible uptake might enable a reduction in the administered dose. The majority of the normal volunteer studies were carried out under fasting conditions, and food intake can influence nicotinamide absorption. These patients are dosed early in the morning, and most show fast and consistent uptake of nicotinamide. We are currently assessing means to improve absorption, and also investigating the use of saliva monitoring instead of measuring plasma concentrations directly.