In vivo nitrosation of amidopyrine in humans: use of 'ethanol effect' for biological monitoring of N-nitrosodimethylamine in urine.
Under normal conditions a possible N-nitrosodimethylamine formation in vivo cannot directly be monitored in urine due to high metabolic conversion rate (greater than 99.9%). Own experiments showed an increased excretion rate (up to 2.4%) if ethanol was administered simultaneously. This model was used for monitoring experiments with respect to in vivo formation of N-nitrosodimethylamine. Amidopyrine, as a compound which is easily nitrosated, was administered (single oral dose of 500 mg) to volunteers. Under the influence of 20-30 g ethanol it was possible to detect N-nitrosodimethylamine in urine. From negative control experiments it must be concluded that this appearance of N-nitrosodimethylamine derives from in vivo nitrosation of the drug. The amount excreted in urine varied between 0.5 and 10 micrograms N-nitrosodimethylamine within 8 h and seemed to be influenced by salivary nitrite concentrations which ranged from 5 to 220 p.p.m. NO-2. In comparison with earlier excretion studies in humans it can be assumed that only 1-2% of the originally formed nitrosamine was found in urine. To our knowledge this is the first time that in vivo formation of N-nitrosodimethylamine was directly shown to occur in humans.
D000632:Aminopyrine / Q000032:analysis* / Q000652:urine; D004128:Dimethylnitrosamine / Q000652:urine*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009566:Nitrates / Q000032:analysis / Q000652:urine; D009573:Nitrites / Q000032:analysis / Q000652:urine; D012463:Saliva / Q000032:analysis*
D009566:Nitrates; D009573:Nitrites; D000632:Aminopyrine; D000431:Ethanol; D004128:Dimethylnitrosamine