Michaelis H C, Clemens C, Kijewski H, Neurath H, Eggert A
Department of Pharmacology and Toxicology, University of Göttingen, Germany.
J Toxicol Clin Toxicol. 1991;29(4):447-58. doi: 10.3109/15563659109025740.
Acute acetonitrile toxicity is mainly dependent on the release of cyanide via hepatic metabolism. Although evaluated in animals, few data are available concerning the toxicokinetic parameters of acetonitrile and acetonitrile-liberated cyanide in human. This paper reports a case of suicidal oral acetonitrile ingestion of about 5 mL without severe symptoms of intoxication in a previously healthy adult male with a body weight of 60 kg. Acetonitrile serum concentrations as well as cyanide blood levels were determined over the whole hospitalization. The elimination half-lives calculated from these data were 32 h for acetonitrile and 15 h for cyanide. After sodium thiosulfate bolus application, the cyanide blood level rapidly decreased to 10% of the initial value, indicating that sodium thiosulfate sufficiently detoxifies acetonitrile-liberated cyanide. Since cyanide levels again increased to maximal values about 4.5 h after sodium thiosulfate application, continued thiosulfate therapy is required as predicted by the long elimination half-lives of acetonitrile and acetonitrile-liberated cyanide. Determination of cyanide and acetonitrile concentrations is recommended for the estimation of optimal individual sodium thiosulfate dosage.
急性乙腈中毒主要取决于通过肝脏代谢释放出氰化物。虽然已在动物身上进行了评估，但关于乙腈和乙腈释放出的氰化物在人体中的毒代动力学参数的数据却很少。本文报告了一例体重60公斤的既往健康成年男性口服约5毫升乙腈自杀但无严重中毒症状的病例。在整个住院期间测定了乙腈血清浓度以及氰化物血药浓度。根据这些数据计算出的消除半衰期，乙腈为32小时，氰化物为15小时。静脉推注硫代硫酸钠后，氰化物血药浓度迅速降至初始值的10%，这表明硫代硫酸钠能充分解毒乙腈释放出的氰化物。由于在应用硫代硫酸钠约4.5小时后氰化物水平再次升至最大值，正如乙腈和乙腈释放出的氰化物较长的消除半衰期所预测的那样，需要持续进行硫代硫酸钠治疗。建议测定氰化物和乙腈浓度以估计最佳个体硫代硫酸钠剂量。
