Scott J C, Stanski D R
J Pharmacol Exp Ther. 1987 Jan;240(1):159-66.
The effect of increasing age on the dose of fentanyl or alfentanil required to produce the same electroencephalographic (EEG) stage was studied in adult male patients. The pharmacokinetic and pharmacodynamic components of each patient's dose-response relationship were evaluated simultaneously. Frequent arterial blood samples drawn during and after an infusion of fentanyl or alfentanil were assayed by radioimmunoassay and permitted determination of each patient's pharmacokinetic profile. The EEG was analyzed by power spectral analysis and a parameter (spectral edge frequency) chosen to quantitate the narcotic-induced EEG slowing. An inhibitory sigmoid Emax pharmacodynamic model related spectral edge frequency to narcotic serum concentrations. The dose requirement of fentanyl or alfentanil decreased significantly with increasing age (a 50% decrease from age 20 to 89). No age-related changes in the pharmacokinetic parameters were found. Brain sensitivity (as determined by EEG changes) did decrease significantly with age. Thus, the decreased dose requirement in the elderly had a pharmacodynamic explanation, using the EEG as a measure of narcotic drug effect.
在成年男性患者中，研究了年龄增长对产生相同脑电图（EEG）阶段所需芬太尼或阿芬太尼剂量的影响。同时评估了每位患者剂量反应关系的药代动力学和药效学成分。在输注芬太尼或阿芬太尼期间及之后采集的频繁动脉血样通过放射免疫分析法进行测定，从而确定每位患者的药代动力学特征。通过功率谱分析对脑电图进行分析，并选择一个参数（频谱边缘频率）来量化麻醉药引起的脑电图减慢。一个抑制性S形Emax药效学模型将频谱边缘频率与麻醉药血清浓度相关联。芬太尼或阿芬太尼的剂量需求随着年龄的增长而显著降低（从20岁到89岁降低了50%）。未发现药代动力学参数有与年龄相关的变化。脑敏感性（通过脑电图变化确定）确实随着年龄的增长而显著降低。因此，以脑电图作为麻醉药效果的衡量指标，老年人剂量需求的降低有药效学方面的解释。
