Ducharme J, Varin F, Bevan D R, Donati F
Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Clin Pharmacokinet. 1993 Jun;24(6):507-18. doi: 10.2165/00003088-199324060-00006.
The effect of early blood sampling on the description of the vecuronium pharmacokinetic-pharmacodynamic relationship was studied following a bolus injection. Sample collection every 10 sec during the first 2 min showed a high concentration peak at 30 to 40 sec, accounting for an important proportion of the total area under the plasma concentration-time curve (AUC). Neglecting it, using only blood samples drawn at 1 and 2 min (limited sampling), led to a significant overestimation of noncompartmentally derived values of mean residence time, clearance, volume of distribution at steady-state and rate of transfer of vecuronium into the effect compartment. Compartmental pharmacokinetics could not be applied to concentration-time curves constructed with early samples, but limited sampling data were fitted to a 2-compartment model. Derived compartmental pharmacokinetic and pharmacokinetic-pharmacodynamic parameters were similar to those obtained noncompartmentally with complete sampling every 10 sec, because back-extrapolation to time zero contributed to the increase in the AUC. However, compartmental analysis does not provide an accurate description of concentration changes following injection.
在静脉推注后，研究了早期采血对维库溴铵药代动力学-药效学关系描述的影响。在前2分钟内每隔10秒采集一次样本，结果显示在30至40秒出现一个高浓度峰值，该峰值在血浆浓度-时间曲线（AUC）下的总面积中占重要比例。忽略该峰值，仅使用在1分钟和2分钟采集的血样（有限采样），会导致对非房室模型得出的平均驻留时间、清除率、稳态分布容积以及维库溴铵向效应室的转运速率值的显著高估。房室药代动力学不适用于用早期样本构建的浓度-时间曲线，但有限采样数据可拟合到二室模型。推导得到的房室药代动力学和药代动力学-药效学参数与每隔10秒进行完整采样用非房室模型得到的参数相似，因为向时间零点的反向外推导致了AUC的增加。然而，房室分析并不能准确描述注射后的浓度变化。
