Neumann H G
Arch Toxicol Suppl. 1979(2):229-38. doi: 10.1007/978-3-642-67265-1_19.
Highly and specifically (3H)-labeled trans-4-dimethylaminostilbene was orally administered to female Wistar rats in doses ranging from 5 X 10(-10) to 2.5 X 10(-4) mol/kg. The following parameters were determined: tissue index in several tissues, binding index of liver proteins, rRNA, DNA, plasma proteins and haemoglobin and stomach proteins. Up to a dose of 2.5 X 10(-6) mol/kg all parameters remained constant, i.e. binding increased proportionately with the dose. It is concluded that simple and linear kinetics prevail and that a pharmacokinetic threshold does not exist in this dose range. At higher doses deviations from linearity were observed, however, the binding index decreased rather than increased with the dose. The results indicate that reactive metabolities are involved in the acute toxic effects observed in the rat stomach and that proximate or ultimate activation products are distributed in the circulation. Their concentration in the target tissue appears not be be specifically high to account for the tissue susceptibility.
将高特异性的（3H）标记反式-4-二甲基氨基芪以5×10^(-10)至2.5×10^(-4)摩尔/千克的剂量口服给予雌性Wistar大鼠。测定了以下参数：几个组织中的组织指数、肝脏蛋白质、rRNA、DNA、血浆蛋白质和血红蛋白以及胃蛋白质的结合指数。在剂量高达2.5×10^(-6)摩尔/千克时，所有参数均保持恒定，即结合与剂量成比例增加。得出的结论是，存在简单的线性动力学，并且在该剂量范围内不存在药代动力学阈值。然而，在较高剂量下观察到偏离线性，结合指数随剂量降低而非增加。结果表明，反应性代谢产物参与了在大鼠胃中观察到的急性毒性作用，并且近端或最终活化产物分布在循环中。它们在靶组织中的浓度似乎并非特别高，不足以解释组织易感性。
