NITROSATION OF PROPRANOLOL UNDER SIMULATED GASTRIC CONDITIONS

Nitrosation of propranolol, a beta-adrenergic blocking drug previously found to react with nitrite in HCl solution yielding a genotoxic nitr osamine, was examined under simulated gastric conditions. In the prese nce of a low concentration of nitrite (2.9 mM) and a therapeutic gastr ic concentration of the drug (5.4 mM), the yield of N-nitrosopropranol ol was higher in simulated gastric juice, which contained both pepsin and thiocyanate, than in distilled water, and at pH 3.5 than at pH 1.0 , A 55 mu M concentration of N-nitrosopropranolol was reached after 18 0 min. It is reasonable to assume that the extremely small amounts of N-nitrosopropranolol formed in the human stomach should not represent a significant carcinogenic risk, but co-formulation of propranolol wit h ascorbic acid, which has been found to minimize the nitrosation reac tion, might be useful to avoid a further, even if minimal, contributio n to the already existing exposure to genotoxic chemicals.