[Comparative studies of the nitrosation behavior of drugs by constant pH value and under simulated stomach conditions].
The nitrosation behaviour of 60 orally administered drugs used in the GDR have been investigated. Only those pharmaceuticals were selected whose active agents are assessed as being nitrosatable by their chemical structures. Amounts of active components and nitrite, dissolved in the gastric juice, did not exceed the concentrations permissible for human stomachs in vivo. After one-hour incubation at pH 2.0 and 37 degrees C ten drugs (Aminophenazone, Ampicilline, Clomipramine, Desipramine, Ethambutole, Imipramine, Noramidopyrinmethansulfonate, Oxacilline, Phenoxymethylpenicilline, Piperazine) proved to be nitrosatable using a colorimetric measuring method. Two of the N-nitroso compounds have been identified as known carcinogens. Structure analysis of the remaining ones is not yet finished. Results still more conforming to in vivo conditions have been obtained for all ten nitrosatable drugs by means of a model system simulating the conditions of the human stomach. The pH changes attending the shifts of pH occurring in the course of the digestive process have a distinct effect on the nitrosation reactions. It is only on such measurements of drug nitrosation that decisions on oral application, calculation of the burdening of the organism by N-nitroso compounds, or estimation of risk should be based.
D000632:Aminopyrine / Q000378:metabolism; D000667:Ampicillin / Q000378:metabolism; D001711:Biotransformation; D002997:Clomipramine / Q000378:metabolism; D003891:Desipramine / Q000378:metabolism; D004177:Dipyrone / Q000378:metabolism; D004977:Ethambutol / Q000378:metabolism; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D009369:Neoplasms / Q000139:chemically induced; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism*; D010068:Oxacillin / Q000378:metabolism; D010406:Penicillins / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism
D009573:Nitrites; D009603:Nitroso Compounds; D010406:Penicillins; D010879:Piperazines; D000632:Aminopyrine; D004177:Dipyrone; D000667:Ampicillin; D004977:Ethambutol; D002997:Clomipramine; D007099:Imipramine; D003891:Desipramine; D010068:Oxacillin
Vergleichende Untersuchungen des Nitrosierungsverhaltens von Arzneimitteln bei konstantem pH-Wert und unter simulierten Magenbedingungen.