Williams D P, Kitteringham N R, Naisbitt D J, Pirmohamed M, Smith D A, Park B K
Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, UK.
Curr Drug Metab. 2002 Aug;3(4):351-66. doi: 10.2174/1389200023337423.
Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into short-lived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.
低分子量有机化学物质可被正常的药物代谢系统转化为对细胞大分子具有内在反应活性的短寿命代谢产物。有直接证据表明，此类化学反应性代谢产物的形成可能在细胞和动物模型中导致诱变、致癌、细胞凋亡和坏死。已证明许多与人类非药理学药物毒性相关的药物在体内或体外都会发生生物活化。因此，我们研究了反应性代谢产物在三种最常见的药物诱导毒性（肝毒性、皮肤反应和血液系统疾病）中所起作用的证据。
