Martyn J A, Leibel W S, Matteo R S
Anesth Analg. 1983 Feb;62(2):160-3.
Combination of pancuronium (Pm) with d-tubocurarine (dTC) or metocurine (mTC) produces potentiation of neuromuscular effects. We tested the hypothesis that this effect is due to decreased plasma protein and/or nonspecific (noncholinergic) tissue binding by one or the other drug such that a greater than expected proportion of unbound drug reaches its neuromuscular site of activity. By varying the concentration of Pm, dTC, and mTC, competitive binding by Pm and dTC or Pm and mTC to plasma constituents was tested in vitro by equilibrium dialysis. Drug interaction and displacement from nonspecific binding sites in tissues was tested in vivo with Pm-mTC combinations. During recovery of mTC-induced neuromuscular paralysis, monitored by evoked twitch tension, 1 mg of Pm was administered intravenously. The twitch height and plasma mTC concentrations before and after Pm administration were noted. The in vitro plasma dTC or mTC binding was not significantly altered by the addition of Pm. Similarly, plasma mTC concentrations in vivo did not increase following the administration of Pm. Thus, there was no displacement of mTC from nonspecific tissue binding sites by Pm. Our in vitro and in vivo experiments both demonstrate that there is no interaction between Pm--dTC and Pm--mTC relative to plasma or tissue binding and thus cannot explain the potentiating effect of the drug combination.
泮库溴铵（Pm）与d - 筒箭毒碱（dTC）或美索曲明（mTC）联合使用会增强神经肌肉效应。我们检验了这样一种假说，即这种效应是由于一种或另一种药物使血浆蛋白和/或非特异性（非胆碱能）组织结合减少，从而使未结合药物到达其神经肌肉活性部位的比例高于预期。通过改变Pm、dTC和mTC的浓度，采用平衡透析法在体外测试了Pm与dTC或Pm与mTC对血浆成分的竞争性结合。用Pm - mTC组合在体内测试了药物相互作用以及从组织中非特异性结合位点的置换情况。在通过诱发抽搐张力监测mTC诱导的神经肌肉麻痹恢复过程中，静脉注射1 mg Pm。记录注射Pm前后的抽搐高度和血浆mTC浓度。添加Pm后，体外血浆dTC或mTC结合没有明显改变。同样，注射Pm后体内血浆mTC浓度没有增加。因此，Pm没有使mTC从非特异性组织结合位点上置换下来。我们的体外和体内实验均表明，Pm - dTC和Pm - mTC在血浆或组织结合方面不存在相互作用，因此无法解释药物组合的增强效应。
