Creedon K A, Suttie J W
Thromb Res. 1986 Oct 15;44(2):147-53. doi: 10.1016/0049-3848(86)90130-1.
Clinical use of antibiotics containing a N-methyl-thiotetrazole (NMTT) side chain has been reported to be associated with an increased incidence of a vitamin K-responsive hypoprothrombinemia. Administration of NMTT to rats decreased the activity of the liver microsomal vitamin K epoxide reductase, increased the liver ratio of vitamin K epoxide to vitamin K, and decreased the rate of metabolism of injected vitamin K epoxide. These responses are the same as those observed following the administration of coumarin anticoagulants. In contrast to the effect of coumarin anticoagulants, NMTT did not inhibit the vitamin K epoxide reductase in vitro. These data suggest that the hypoprothrombinemia which has been observed following use of these antibiotics results from the inactivation of the liver vitamin K epoxide reductase by NMTT or a NMTT metabolite.
据报道，含有N-甲基硫代四唑（NMTT）侧链的抗生素在临床使用中与维生素K反应性低凝血酶原血症的发生率增加有关。给大鼠施用NMTT会降低肝脏微粒体维生素K环氧化物还原酶的活性，增加肝脏中维生素K环氧化物与维生素K的比例，并降低注射的维生素K环氧化物的代谢速率。这些反应与施用香豆素抗凝剂后观察到的反应相同。与香豆素抗凝剂的作用相反，NMTT在体外不抑制维生素K环氧化物还原酶。这些数据表明，使用这些抗生素后观察到的低凝血酶原血症是由NMTT或NMTT代谢产物使肝脏维生素K环氧化物还原酶失活所致。
