Hermann D J, Egan T D, Muir K T
Pharsight, Cary, NC 27511, USA.
Clin Pharmacol Ther. 1999 May;65(5):511-8. doi: 10.1016/S0009-9236(99)70070-6.
Remifentanil is a new, short-acting, rapidly metabolized opioid. Because remifentanil is metabolized in blood and tissues by nonspecific esterases, there is a substantial difference between arterial and venous remifentanil concentrations. This difference may greatly affect the estimation of pharmacokinetic and pharmacodynamic parameters.
To assess the effects of sampling site on the pharmacokinetic and pharmacodynamic characteristics of remifentanil.
Ten healthy female subjects received intravenous remifentanil at an infusion rate of 3 microg/kg/min for 10 minutes. Serial blood samples were collected during and after drug administration from the radial artery and antecubital vein. A spectral edge measure was derived from the processed electroencephalographic and used as a measure of opioid effect.
Venous concentrations were lower than arterial concentrations during the infusion of remifentanil. Pharmacokinetic parameters estimated from venous and arterial data differed significantly. When arterial concentrations were plotted against electroencephalographic effect, a classic counterclockwise hysteresis loop was observed, indicating a time-lag between changes in concentration and changes in effect. However, concentrations from venous blood produced a clockwise hysteresis loop that would classically suggest the development of acute tolerance.
If this study had been conducted with venous samples alone, inappropriate conclusions such as acute tolerance could have been inferred. When designing studies to measure the acute time course (ie, non-steady state) of concentration and effect, the potential effects of sampling site on pharmacokinetic and pharmacodynamic characteristics must be carefully considered, particularly when the arteriovenous drug concentration difference is large.
瑞芬太尼是一种新型短效、快速代谢的阿片类药物。由于瑞芬太尼在血液和组织中由非特异性酯酶代谢，动脉血和静脉血中瑞芬太尼浓度存在显著差异。这种差异可能会极大地影响药代动力学和药效学参数的估计。
评估采样部位对瑞芬太尼药代动力学和药效学特征的影响。
10名健康女性受试者以3μg/kg/min的输注速率静脉输注瑞芬太尼10分钟。在给药期间和给药后，从桡动脉和肘前静脉采集系列血样。从处理后的脑电图中得出频谱边缘测量值，并将其用作阿片类药物效应的指标。
在输注瑞芬太尼期间，静脉血浓度低于动脉血浓度。根据静脉血和动脉血数据估算的药代动力学参数有显著差异。当将动脉血浓度与脑电图效应作图时，观察到一个典型的逆时针滞后环，表明浓度变化和效应变化之间存在时间滞后。然而，静脉血浓度产生了一个顺时针滞后环，这通常表明急性耐受性的发展。
如果仅使用静脉血样本进行这项研究，可能会得出诸如急性耐受性等不恰当的结论。在设计测量浓度和效应的急性时程（即非稳态）的研究时，必须仔细考虑采样部位对药代动力学和药效学特征的潜在影响，特别是当动静脉药物浓度差异较大时。
