Frank N, Christmann A, Frei E
German Cancer Research Center, Division of Molecular Toxicology, Heidelberg.
Toxicology. 1995 Jan 6;95(1-3):113-22. doi: 10.1016/0300-483x(94)02890-7.
The pharmacokinetics of the antitoxic and anticarcinogenic compounds diethyldithiocarbamate, prolinedithiocarbamate and sarcosinedithiocarbamate were compared in rats. The bioavailability, the distribution in the organism, the oxidation to thiuramdisulfides, the cleavage to CS2 and the excretion in urine and bile were investigated. The results showed different behaviour of the three compounds. The more toxic diethyldithiocarbamate had a short in vivo half-life, was oxidized to tetraethylthiuramdisulfide in blood, and was metabolized to high yields of CS2 in 24 h. In contrast, prolinedithiocarbamate was more stable in vivo, was found predominantly in the urinary tract and was excreted in urine. The differences could not be explained by the presence of the carboxy group in the latter dithiocarbamate, since sarcosinedithiocarbamate, which also contains a carboxy group, behaved like diethyldithiocarbamate.
在大鼠体内比较了抗毒和抗癌化合物二乙基二硫代氨基甲酸盐、脯氨酸二硫代氨基甲酸盐和肌氨酸二硫代氨基甲酸盐的药代动力学。研究了它们的生物利用度、在体内的分布、氧化为秋兰姆二硫化物、裂解为二硫化碳以及在尿液和胆汁中的排泄情况。结果显示这三种化合物表现出不同的行为。毒性更强的二乙基二硫代氨基甲酸盐在体内半衰期较短，在血液中氧化为四乙基秋兰姆二硫化物，并在24小时内代谢生成高产率的二硫化碳。相比之下，脯氨酸二硫代氨基甲酸盐在体内更稳定，主要存在于尿路中并通过尿液排泄。后一种二硫代氨基甲酸盐中羧基的存在无法解释这些差异，因为同样含有羧基的肌氨酸二硫代氨基甲酸盐的行为与二乙基二硫代氨基甲酸盐相似。
