Metabolites of the radiosensitizer nicotinamide are unlikely to contribute to the degree of emesis observed with the parent drug.

Nicotinamide is a potent radiosensitizer currently employed in the treatment of cancer of the bladder, head, and neck. Unfortunately, nicotinamide is also a potent emetic at the concentrations required for radiosensitization. Previously, we have demonstrated that nicotinamide-induced emesis is the direct result of decreased spontaneous peristaltic activity in the ileum. However, the effect of nicotinamide's metabolites on peristaltic activity have not been investigated, although several studies have unsuccessfully attempted to correlate the degree of emesis with the levels of the metabolites in plasma. Isolated rat ileum rings and rat tail arteries were perfused with oxygenated Krebs solution in an organ bath. Nicotinamide, 1-methynicotinamide, or N-oxide nicotinamide were introduced to the perfusate and changes in amplitude of spontaneous peristaltic activity or phenylephrine-induced vasoconstriction recorded. Nicotinamide inhibited peristalsis in the ileum and agonist-induced vasoconstriction in the rat tail arteries, as previously observed. However, the primary metabolites of nicotinamide were without effect. Gut smooth muscle and rat tail artery are sensitive to the relaxant effects of nicotinamide. The primary metabolites of nicotinamide are not vasoactive and do not blunt either spontaneous or agonist-induced contraction and are thus unlikely to contribute to the degree of emesis observed following nicotinamide administration.