Wingard L B, Cook D R
Br J Anaesth. 1976 Sep;48(9):839-45. doi: 10.1093/bja/48.9.839.
The pharmacodynamics of neuromuscular transmission, following blockade by a single i.v. dose of tubocurarine (dtc) in humans, were simulated from experimental serum dtc concentration versus time data and serum dtc concentration versus percentage recovery data. Good agreement was obtained between the simulated and experimental time course of recovery at five different therapeutic doses. The initial apparent volume of distribution (Vapp) of dtc was approximately the same as the serum volume and appeared to increase with the size of the dose. These results were consistent with the suggestion that a greater fraction of the dose of dtc was distributed in non-vascular spaces or bound to tissue at larger doses. A pharmacodynamic working model using an average Vapp of 2848 ml simulated times up to 40% recovery within 15-20% error for doses of dtc of 0.30 mg/kg or less.
根据人单次静脉注射筒箭毒碱(dtc)后的实验血清dtc浓度与时间数据以及血清dtc浓度与恢复百分比数据,模拟了神经肌肉传递的药效学。在五个不同治疗剂量下,模拟的恢复时间进程与实验结果取得了良好的一致性。dtc的初始表观分布容积(Vapp)与血清容积大致相同,且似乎随剂量大小而增加。这些结果与以下观点一致:在较大剂量时,dtc剂量的更大比例分布在非血管空间或与组织结合。使用平均Vapp为2848 ml的药效学工作模型,对于0.30 mg/kg或更低剂量的dtc,在15 - 20%的误差范围内模拟了高达40%恢复的时间。