Newman R A, Farquhar D
Department of Medical Oncology, U.T.M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Invest New Drugs. 1987;5(3):267-71. doi: 10.1007/BF00175297.
In recent phase 1 clinical trials, caracemide [N-acetyl-N-(methylcarbamoyloxy)-N-methylurea; NSC-253272] has demonstrated a marked potential to produce severe central nervous system (CNS) toxicity. Recent in vitro studies of this antitumor agent have presented indirect evidence indicating that methyl isocyanate is a likely metabolite which results from incubation of caracemide with either phosphate buffer or human plasma. This report presents evidence that methyl isocyanate is formed from caracemide in a concentration- and time-dependent manner. These data implicate the caracemide-mediated formation of methyl isocyanate as at least a plausible explanation for the CNS toxicity exhibited by this drug.
在最近的1期临床试验中，卡醋胺[N-乙酰基-N-(甲基氨基甲酰氧基)-N-甲基脲；NSC-253272]已显示出产生严重中枢神经系统（CNS）毒性的显著潜力。最近对这种抗肿瘤药物的体外研究提供了间接证据，表明异氰酸甲酯是卡醋胺与磷酸盐缓冲液或人血浆孵育后可能产生的代谢产物。本报告提供的证据表明，异氰酸甲酯以浓度和时间依赖性方式由卡醋胺形成。这些数据表明，卡醋胺介导的异氰酸甲酯形成至少是该药物所表现出的中枢神经系统毒性的一个合理的解释。
