三种苯二氮䓬类药物的体外羟基化作用

Hydroxylation of three benzodiazepines in vitro.

作者信息

Mussini E, Marcucci F, Airoldi L, Facchinetti T, Garattini S

出版信息

J Pharm Sci. 1977 Oct;66(10):1482-3. doi: 10.1002/jps.2600661035.

Abstract

Three structurally related benzodiazepines were studied as substrates for hydroxylation by liver microsomal enzymes of rats and mice. The Vmax was comparable for dechlorodesmethyldiazepam, desmethyldiazepam, and 2'-chlorodesmethyldiazepam in the two animal species. The apparent Km decreased from dechlorodesmethyldiazepam to 2'-chlorodesmethyldiazepam for liver microsomal enzymes from both animal species. The hydroxylation of desmethyldiazepam and 2'-chlorodesmethyldiazepam yielded two pharmacologically active metabolites, oxazepam and lorazepam, respectively.

摘要

研究了三种结构相关的苯二氮䓬类药物作为大鼠和小鼠肝脏微粒体酶羟基化反应的底物。在这两种动物中，去氯去甲基地西泮、去甲地西泮和2'-氯去甲基地西泮的Vmax相当。对于这两种动物的肝脏微粒体酶，表观Km从去氯去甲基地西泮到2'-氯去甲基地西泮逐渐降低。去甲地西泮和2'-氯去甲基地西泮的羟基化反应分别产生了两种具有药理活性的代谢产物，即奥沙西泮和劳拉西泮。