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Updated: Aug 19, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Nitrosation of propranolol under simulated gastric conditions
G Brambilla1, A Martelli, E Sottofattori
1Institute of Pharmacology, University of Genoa, Italy.
Abstract:
Nitrosation of propranolol, a beta-adrenergic blocking drug previously found to react with nitrite in HCl solution yielding a genotoxic nitrosamine, was examined under simulated gastric conditions. In the presence of a low concentration of nitrite (2.9 mM) and a therapeutic gastric concentration of the drug (5.4 mM), the yield of N-nitrosopropranolol 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 microM concentration of N-nitrosopropranolol was reached after 180 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 with ascorbic acid, which has been found to minimize the nitrosation reaction, might be useful to avoid a further, even if minimal, contribution to the already existing exposure to genotoxic chemicals.
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