Smith C E, van Miert M M, Parker C J, Hunter J M
University Department of Anaesthesia, Liverpool, UK.
Anaesthesia. 1997 Sep;52(9):833-41. doi: 10.1111/j.1365-2044.1997.195-az0331.x.
We have compared the pharmacokinetics of cisatracurium with atracurium when given by bolus dose followed by continuous infusion. Twenty healthy patients were anaesthetised with thiopentone, midazolam, fentanyl and 70% nitrous oxide in oxygen. Ten patients (Group C) were randomly allocated to receive cisatracurium 0.1 mg.kg-1 and 10 patients (Group A) were given atracurium 0.5 mg.kg-1. Neuromuscular block was monitored using a mechanomyograph. When the first twitch of the train-of-four had recovered to 5% of control, an infusion of cisatracurium 3 micrograms.kg-1.min-1 was started in Group C and an infusion of atracurium 10 micrograms.kg-1.min-1 was started in Group A. The infusion rates were adjusted to maintain the first twitch of the train-of-four at 5% of control. The times to 90% and maximum depression of the first twitch of the train-of-four were significantly longer after cisatracurium than atracurium (2.2 and 3.4 min compared with 1.3 and 1.8 min, respectively; p < 0.01 in each instance). No significant differences were found in recovery parameters between the two groups. Blood samples were taken at regular intervals following the bolus, during the infusion and for 8 h thereafter. The plasma samples were analysed using high-performance liquid chromatography for cisatracurium and atracurium (using a method which distinguishes between the three geometric isomer groups), laudanosine and monoquaternary alcohol. The results were analysed using the Non-linear Mixed Effects Model program. A two-compartment model was fitted to the data. The different isomer groups of atracurium have different pharmacokinetics, the trans-trans group having the highest clearance (1440 ml.min-1) and the cis-cis group the lowest (499 ml.min-1). The clearance of cisatracurium (425 ml.min-1) is less than that of cis-cis atracurium and its elimination half-life is longer (34.9 min and 21.9 min, respectively). The plasma concentration of laudanosine after cisatracurium was one-fifth of that after atracurium.
我们比较了单次静脉注射后持续输注顺式阿曲库铵和阿曲库铵的药代动力学。20名健康患者用硫喷妥钠、咪达唑仑、芬太尼和70%氧化亚氮与氧气混合进行麻醉。10名患者（C组）随机分配接受0.1mg/kg的顺式阿曲库铵，10名患者（A组）给予0.5mg/kg的阿曲库铵。使用肌动描记器监测神经肌肉阻滞。当四个成串刺激的第一个颤搐恢复到对照值的5%时，C组开始以3μg·kg-1·min-1的速率输注顺式阿曲库铵，A组开始以10μg·kg-1·min-1的速率输注阿曲库铵。调整输注速率以维持四个成串刺激的第一个颤搐在对照值的5%。顺式阿曲库铵后四个成串刺激的第一个颤搐达到90%抑制和最大抑制的时间明显长于阿曲库铵（分别为2.2分钟和3.4分钟，而阿曲库铵为1.3分钟和1.8分钟；每次p<0.01）。两组之间在恢复参数方面未发现显著差异。在单次注射后、输注期间以及此后8小时内定期采集血样。使用高效液相色谱法分析血浆样本中的顺式阿曲库铵和阿曲库铵（使用一种区分三种几何异构体组的方法）、劳丹诺辛和单季铵醇。使用非线性混合效应模型程序分析结果。对数据拟合二室模型。阿曲库铵的不同异构体组具有不同的药代动力学，反-反组清除率最高（1440ml·min-1），顺-顺组最低（499ml·min-1）。顺式阿曲库铵的清除率（425ml·min-1）低于顺-顺式阿曲库铵，其消除半衰期更长（分别为34.9分钟和21.9分钟）。顺式阿曲库铵后血浆劳丹诺辛浓度是阿曲库铵后的五分之一。
