Agoston S, Crul E J, Kersten U W, Houwertjes M C, Scaf A H
Acta Anaesthesiol Scand. 1977;21(1):24-30. doi: 10.1111/j.1399-6576.1977.tb01188.x.
The renal and hepatic elimination and biotransformation, as well as the relation between disposition and duration of action of pancuronium and two of its analogues, dacuronium and ORG.6368, have been investigated in the cat. In pharmacokinetic studies, appreciable amounts of the latter two compounds were found in the urine, bile and liver 8 h after their intravenous administration. Various proportions of the injected dose of the respective drugs were metabolized. In another series of experiments it was shown that the early hepatic uptake (during the first 3 min after the injection) of ORG.6368 was significantly greater than that of dacuronium and pancuronium. The intensity and duration of action of the neuromuscular blocking effect of the three compounds were studied after intravenous and "close" intraarterial injection. On the basis of these pharmacokinetic and neuromuscular studies, it was concluded that the short duration of action of ORG.6368 is due primarily to its early hepatic uptake. The possibility cannot be excluded, however, that differences in the kinetics of the drug action of ORG.6368 and the other two compounds also contributed significantly to the differences seen in the duration of action of these compounds.
已在猫身上研究了泮库溴铵及其两种类似物达库溴铵和ORG.6368的肾脏和肝脏消除、生物转化，以及处置与作用持续时间之间的关系。在药代动力学研究中，静脉注射后8小时，在尿液、胆汁和肝脏中发现了相当数量的后两种化合物。各自药物的注射剂量有不同比例被代谢。在另一系列实验中表明，ORG.6368的早期肝脏摄取（注射后最初3分钟内）明显大于达库溴铵和泮库溴铵。静脉注射和“近距离”动脉内注射后，研究了这三种化合物神经肌肉阻滞作用的强度和持续时间。基于这些药代动力学和神经肌肉研究得出结论，ORG.6368作用持续时间短主要是由于其早期肝脏摄取。然而，不能排除ORG.6368与其他两种化合物药物作用动力学差异也对这些化合物作用持续时间差异有显著贡献的可能性。
