Remifentanil versus alfentanil - Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers
Remifentanil versus alfentanil - Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers
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DOI：
10.1097/00000542-199604000-00009
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发表时间：
1996-04-01
期刊：
影响因子：
8.8
通讯作者：
Shafer, SL
中科院分区：
文献类型：
--
作者：
Egan, TD;Minto, CF;Shafer, SL
背景：瑞芬太尼是一种酯酶代谢的阿片类药物，清除迅速。本研究的目的是比较瑞芬太尼和阿芬太尼在健康成年男性志愿者中的药代动力学和药效学。10名志愿者采用随机、开放、交叉设计，分别输注瑞芬太尼和阿芬太尼，分析动脉血样品以确定药物血药浓度，采用脑电图作为药物效应的测量，采用矩分析、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表征药代动力学。在处理原始脑电图以获得谱边缘参数后，采用效应室抑制最大效应模型表征药效学。这两种药物在稳态分布容积（VDss）方面相似，但瑞芬太尼的中心清除率（CL（c））显著更大。雷米芬太尼的NONMEM分析群体药代动力学参数包括CL（c）2.91。min（-1），VDss为21.81，终末半衰期为35.1 min，阿芬太尼的相应NONMEM参数为0.361。在药效学上，两种药物在血液和效应部位浓度之间平衡所需的时间方面相似，如瑞芬太尼的T（12）k（eo）为1.6 min和阿芬太尼的0.96 min所证明的，然而，瑞芬太尼的效力是阿芬太尼的19倍，50%最大效应的有效浓度为19.9 ng。ml（-1）与375.9 ng。结论：与阿芬太尼相比，瑞芬太尼清除率高，稳态分布容积小，导致输注结束后血药浓度迅速下降。除了瑞芬太尼的效力高出近20倍（如果考虑阿芬太尼在全血和血浆之间的分配，则为30倍）之外，药物的药效学相似。
Background: 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.Methods: 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.Results Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VDss), but remifentanil's central clearance (CL(c)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CL(c) of 2.91 . min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min, Corresponding NONMEM parameters for alfentanil are 0.361 . 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(eo) for remifentanil of 1.6 min 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 . ml(-1) versus 375.9 ng . ml(-1) for alfentanil.Conclusions: 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.