Ziebarth D
Arch Geschwulstforsch. 1981;51(7):587-95.
Out of 61 drugs, considered to be potentially nitrosatable on the basis of their chemical structure and being used for oral administration in the GDR, ten (Aminophenazone, Ampicilline, Clomipramine, Desipramine, Ethambutole, Imipramine, Noramidopyrinemethansulfonate, Oxacilline, Phenoxymethylpenicilline, Piperazine) have been nitrosated in vitro under simulated conditions of the human stomach. Each compound demonstrated an individual nitrosation behaviour. Only two of the N-nitrosocompounds formed could be identified as well known carcinogens. The chemical structure of the others are unknown yet. Using ascorbic acid as inhibitor, an inhibition of nitrosation could be reached in all cases, but even with high amounts the inhibition was not complete. In order to exclude or, least to diminish a possible carcinogenic risk of endogenically formed N-nitrosocompounds from drugs to humans, drugs orally administered and forming carcinogenic N-nitrosocompounds should be replaced by non-nitrosatable ones. Formulations of all other nitrosatable drugs should contain sufficient amounts of ascorbic acid, provided, that the pharmacological quality of the drug is not deteriorated to any greater extent.
在民主德国,根据化学结构被认为可能会发生亚硝化反应且用于口服的61种药物中,有10种(氨基苯乙酮、氨苄青霉素、氯米帕明、地昔帕明、乙胺丁醇、丙咪嗪、甲磺酸氨基比林、苯唑西林、苯氧甲基青霉素、哌嗪)在模拟人体胃部的条件下进行了体外亚硝化反应。每种化合物都表现出独特的亚硝化行为。所形成的N-亚硝基化合物中只有两种可被鉴定为已知致癌物。其他化合物的化学结构尚不清楚。使用抗坏血酸作为抑制剂,在所有情况下都能实现亚硝化反应的抑制,但即使使用大量抗坏血酸,抑制也不完全。为了排除或至少降低药物内源性形成的N-亚硝基化合物对人类可能产生的致癌风险,口服并形成致癌性N-亚硝基化合物的药物应被不可亚硝化的药物替代。所有其他可亚硝化药物的制剂应含有足够量的抗坏血酸,前提是药物的药理性质不会受到太大程度的损害。