Schlemmer K H, Eisenbrand G
Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Fed. Rep. of Germany.
Arzneimittelforschung. 1988 Sep;38(9):1365-8.
In an ex-vivo study, nitrosation of bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) in human gastric fluid under conditions of high dietary nitrate intake was investigated. 26 healthy volunteers received 200 mg of nitrate in a vegetable during a standard breakfast. Nitrite values in saliva were significantly increased 2 to 3 h after nitrate intake. In contrast, nitrite levels in gastric fluid sampled 3 h after nitrate intake remained in the low concentration range of less than or equal to 1.7 micrograms/No2-/ml. Incubation of gastric fluid samples at 37 degrees C with the recommended maximum single oral dose of bromhexine (16 mg/100 ml) or an equimolar concentration of aminophenazone revealed in 4/26 cases formation of N-nitrosomethylcyclohexylamine from bromhexine at barely detectable levels. In contrast, aminophenazone generated N-nitrosodimethylamine at a very high rate, resulting in yields of greater than 50% in several samples. In view of the average daily background exposure to preformed nitrosamines in foods (0.5-1 microgram/capita), according to these results the possible contribution of in-vivo nitrosation of bromhexine corresponds at best to 10% in addition to the daily background exposure and therefore can be regarded as negligible.
在一项体外研究中，研究了在高膳食硝酸盐摄入条件下，人胃液中溴己新（N-甲基-N-环己基-(2-氨基-3,5-二溴苄基)-氯化铵）的亚硝化作用。26名健康志愿者在标准早餐期间食用了一份蔬菜，其中含有200毫克硝酸盐。摄入硝酸盐后2至3小时，唾液中的亚硝酸盐值显著升高。相比之下，摄入硝酸盐3小时后采集的胃液中的亚硝酸盐水平仍处于小于或等于1.7微克/亚硝酸根/毫升的低浓度范围内。将胃液样本在37℃下与推荐的最大单次口服剂量的溴己新（16毫克/100毫升）或等摩尔浓度的氨基比林一起孵育，结果显示，在26个病例中有4个病例中，溴己新仅在难以检测到的水平上生成了N-亚硝基甲基环己胺。相比之下，氨基比林以非常高的速率生成N-亚硝基二甲胺，在几个样本中的产率超过50%。鉴于食物中预先形成的亚硝胺的平均每日背景暴露量为（0.5-1微克/人），根据这些结果，溴己新体内亚硝化作用的可能贡献除每日背景暴露量外，充其量仅相当于10%，因此可被视为可忽略不计。
