Egan T D, Minto C F, Hermann D J, Barr J, Muir K T, Shafer S L
Palo Alto Veterans Administration Medical Center, Palo Alto, California, USA.
Anesthesiology. 1996 Apr;84(4):821-33. doi: 10.1097/00000542-199604000-00009.
Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers.
Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model.
Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil.
Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar.
瑞芬太尼是一种经酯酶代谢的阿片类药物，清除迅速。本研究的目的是对比瑞芬太尼和阿芬太尼在健康成年男性志愿者体内的药代动力学和药效学。
10名志愿者在不同的研究时段接受瑞芬太尼和阿芬太尼输注，采用随机、开放标签交叉设计。分析动脉血样本以测定药物血药浓度。采用脑电图作为药物效应的指标。药代动力学通过矩量法、非线性混合效应模型（NONMEM）群体分析和上下文敏感半衰期计算机模拟进行表征。对原始脑电图进行处理以获得频谱边缘参数后，药效学采用效应室、抑制性最大效应模型进行表征。
在药代动力学方面，两种药物在稳态分布容积（VD(SS)）方面相似，但瑞芬太尼的中央清除率（CLc）显著更高。瑞芬太尼的NONMEM分析群体药代动力学参数包括CLc为2.9 l x min(-1)、VDss为21.81、终末半衰期为35.1分钟。阿芬太尼相应的NONMEM参数为0.36 l x min(-1)、34.11和94.5分钟。在药效学方面，两种药物在血液与效应部位浓度达到平衡所需时间方面相似，瑞芬太尼的T(12)k(e0)为0.75分钟[校正后]，阿芬太尼为0.96分钟。然而，瑞芬太尼的效价比阿芬太尼高19倍，产生50%最大效应的有效浓度为19.9 ng x ml(-1)，而阿芬太尼为375.9 ng x ml(-1)。
与阿芬太尼相比，瑞芬太尼的高清除率及其较小的稳态分布容积，导致输注结束后血药浓度迅速下降。除瑞芬太尼的效价高近20倍（如果考虑阿芬太尼在全血和血浆之间的分配，则高30倍）外，两种药物在药效学上相似。
