Research letterFormation of nitroso compounds and mutagens from cinnarizine, ethambutol, PIROMIDIC ACID (cas 19562-30-2), pyridinol carbamate and tiaramide by drug/nitrite interaction

Add time:08/25/2019    Source:sciencedirect.com

The formation of nitroso compounds and mutagens from 5 nitrogen-containing drugs (cinnarizine, ethambutol, piromidic acid, pyridinol carbamate and tiaramide) by drug/nitrite interaction was examined. On the reaction of 50 mM drug and 500 mM nitrite at pH 3.0–3.4 and 37°C for 4 h, the considerable formation of nitroso compounds was observed for ethambutol, cinnarizine and pyridinol carbamate. The reaction product of pyridinol carbamate and nitrite was remarkably mutagenic to Salmonella typhimurium TA100 in the absence of S-9 mix. Under conditions presumed to resemble those in the stomach after ingestion of a therapeutic dose of the drug, the formation of nitroso compounds was observed for ethambutol and significant mutagenicity was detected in the reaction product of pyridinol carbamate.

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