Tartaglione T A, Duma R J, Qureshi G D
Antimicrob Agents Chemother. 1986 Jul;30(1):73-7. doi: 10.1128/AAC.30.1.73.
The in vitro effects of aztreonam on platelet aggregation were compared with those of cefotaxime, moxalactam, piperacillin, and carbenicillin. In addition, the in vivo effects of intravenously administered aztreonam on blood coagulation and platelet function were examined in 10 normal male volunteers in a randomized crossover study. In vitro, at concentrations of greater than 6.25 mM (2.7 mg/ml), aztreonam inhibited ADP-induced platelet aggregation in a dose-dependent manner. The effect was less than that produced by equimolar concentrations of cefotaxime, moxalactam, piperacillin, or carbenicillin. At all concentrations tested, aztreonam and cefotaxime inhibited epinephrine-induced aggregation least. All antibiotics inhibited collagen-induced aggregation, but only at inordinately high concentrations (25 mM). In vivo studies in 10 male subjects, randomly infused intravenously with 2 g of aztreonam or saline placebo every 6 h for 21 consecutive doses in a single-blind crossover study, revealed no evidence of bleeding or visible adverse side effects. Although plasma coagulation and platelet adhesion remained within normal limits in all subjects throughout the study, inhibition of ADP-induced platelet aggregation significantly (P less than 0.0001) increased on days 3 and 6, but still was below 40%. With the exception of one subject who had a mean template bleeding time of 7.3 min (normal, 2 to 7 min at 95% confidence limits) on day 6 of aztreonam administration, all volunteers exhibited bleeding times within the normal range. No abnormalities in platelet morphology were observed. Mean peak serum aztreonam concentrations on days 1 and 6 were 90.1 +/- 16.7 and 95.9 +/- 13.7 micrograms/ml, respectively; accumulation did not occur. Thus, in normal volunteers, aztreonam produced no significant recognizable abnormalities of hemostasis after 6 days of maximal recommended doses.
将氨曲南对血小板聚集的体外效应与头孢噻肟、拉氧头孢、哌拉西林和羧苄西林的效应进行了比较。此外，在一项随机交叉研究中，对10名正常男性志愿者静脉注射氨曲南后的体内凝血和血小板功能效应进行了检测。在体外，当浓度大于6.25 mM（2.7 mg/ml）时，氨曲南以剂量依赖的方式抑制ADP诱导的血小板聚集。其效应小于等摩尔浓度的头孢噻肟、拉氧头孢、哌拉西林或羧苄西林所产生的效应。在所有测试浓度下，氨曲南和头孢噻肟对肾上腺素诱导的聚集抑制作用最小。所有抗生素均抑制胶原诱导的聚集，但仅在极高浓度（25 mM）时。在一项单盲交叉研究中，对10名男性受试者进行体内研究，每6小时随机静脉输注2 g氨曲南或生理盐水安慰剂，连续21剂，未发现出血或明显不良副作用的证据。尽管在整个研究过程中所有受试者的血浆凝血和血小板黏附均保持在正常范围内，但在第3天和第6天，ADP诱导的血小板聚集抑制作用显著增加（P小于0.0001），但仍低于40%。除了一名在氨曲南给药第6天平均模板出血时间为7.3分钟（正常范围为2至7分钟，95%置信限）的受试者外，所有志愿者的出血时间均在正常范围内。未观察到血小板形态异常。第1天和第6天氨曲南血清平均峰值浓度分别为90.1±16.7和95.9±13.7微克/毫升；未发生蓄积。因此，在正常志愿者中，在最大推荐剂量给药6天后，氨曲南未产生明显可识别的止血异常。
