NICOTINAMIDE PHARMACOKINETICS IN PATIENTS

Pharmacokinetic analyses were performed on blood samples of 12 patient s undergoing treatment with nicotinamide, hyperthermia and radiation t herapy for a variety of recurrent/metastatic cancers. Escalating oral doses of 3, 4, 5, 6 and 10 g of nicotinamide showed a linear relations hip between maximum recorded plasma concentrations and the dose in gra ms (correlation coefficient, r = 0.91). Maximum plasma levels were obs erved by 30 min in most patients ingesting up to 6 g of nicotinamide. In marked contrast, five out of six patients ingesting 10 g of nicotin amide demonstrated increasing plasma levels at least up to 3 h post-in gestion. Doses up to 6 g were well tolerated and resulted in average m aximum recorded plasma levels (mean +/- 1 SEM) of 156.4 +/- 33.6 mu g/ ml. Doses of 10 g were generally not well tolerated, but a high plasma level was maintained on average for at least 4 h. Plasma concentratio ns of the above order have been previously associated with maximal enh ancement of radiation damage in mouse tumor models. This suggests that radiosensitization can be expected to occur in human tumors following oral administration of a safe and well tolerated dose of 6 g. However , at higher doses (i.e., 10 g), the pharmacokinetics, and perhaps radi osensitization, may differ markedly.