Genotoxic activities of drug-nitrite interaction products.
At first 28 orally administered drugs, considered to be potentially nitrosatable on the basis of their chemical structure, have been nitrosated with nitrite under simulated stomach conditions. A maximum daily dose of each drug was incubated with a nitrite concentration that can be found after a normal meal in the stomach at 37 degrees C over 1 h. Reaction was started at pH 6.8-7.0 and stopped at pH 2.0, so we had the same pH change that occurs in the stomach. Secondly the genotoxic activities of drug-nitrite interaction products were tested by the umu-test with Salmonella typhimurium TA 1535/pSK1002 as tester strain in the presence and absence of metabolic activation. By the umu-test, among the nitrosation products of drugs examined 22 products showed genotoxicity at different levels. Other six products showed negative results by the umu-test.
Ozhan
Gül
G
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Alpertunga
Buket
B
D000284:Administration, Oral; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006863:Hydrogen-Ion Concentration; D009152:Mutagenicity Tests; D009573:Nitrites / Q000737:chemistry*; D009603:Nitroso Compounds / Q000378:metabolism* / Q000633:toxicity*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics
D009573:Nitrites; D009603:Nitroso Compounds; D004364:Pharmaceutical Preparations