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 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.
Brambilla
G
G
Institute of Pharmacology, University of Genoa, Italy.
Martelli
A
A
Sottofattori
E
E
D005750:Gastric Juice; D006801:Humans; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009573:Nitrites / Q000737:chemistry* / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D011433:Propranolol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D013861:Thiocyanates
D009573:Nitrites; D009602:Nitrosamines; D013861:Thiocyanates; C037601:N-nitrosopropranolol; D011433:Propranolol; D010434:Pepsin A; D006851:Hydrochloric Acid