Singleton M A, Rosen J I, Fisher D M
Department of Anesthesia, University of California, San Francisco 94143-0648.
Br J Anaesth. 1988 May;60(6):619-22. doi: 10.1093/bja/60.6.619.
The pharmacokinetics of fentanyl were determined in seven elderly (71-82 yr) and seven younger adults (18-41 yr) anaesthetized with thiopentone, nitrous oxide in oxygen and morphine. Fentanyl was administered as a 2-min i.v. infusion at doses of 15 micrograms kg-1 for elderly patients and 20 micrograms kg-1 for the younger patients. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Fentanyl concentration, per microgram kg-1 administered, was higher in elderly than in young patients at 2 min (7.73 +/- 3.14 v. 4.54 +/- 1.83 ng ml-1 (mean +/- SD), respectively) and at 4 min after the start of infusion (3.26 +/- 1.44 v. 1.78 +/- 0.72 ng ml-1, respectively). Concentrations were similar at all other sampling times. Pharmacokinetic variables were determined by non-compartmental techniques. Total plasma clearance was similar for the two age groups. Volume of distribution at steady-state (VDss) was smaller in elderly patients (1.36 +/- 0.44 v. 2.27 +/- 0.82 litre kg-1). Despite age-related changes in VDss, plasma fentanyl concentrations for the two groups were similar throughout the 4-h sampling period except immediately following administration. These results suggest that, if there are age-related differences in response to fentanyl, the likely pharmacokinetic explanation is the higher concentration of fentanyl in the elderly immediately following its administration.
在七名老年患者(71 - 82岁)和七名年轻成年人(18 - 41岁)中,研究了芬太尼的药代动力学。这些患者均用硫喷妥钠、氧化亚氮和氧气以及吗啡进行麻醉。芬太尼以静脉输注2分钟的方式给药,老年患者剂量为15微克/千克,年轻患者剂量为20微克/千克。采集4小时的血浆样本,并用放射免疫分析法测定芬太尼浓度。按每千克体重给药的微克数计算,在给药2分钟时(分别为7.73±3.14对4.54±1.83纳克/毫升(平均值±标准差))以及输注开始后4分钟时(分别为3.26±1.44对1.78±0.72纳克/毫升),老年患者体内的芬太尼浓度高于年轻患者。在所有其他采样时间,浓度相似。药代动力学变量通过非房室技术测定。两个年龄组的总血浆清除率相似。老年患者的稳态分布容积(VDss)较小(1.36±0.44对2.27±0.82升/千克)。尽管VDss存在与年龄相关的变化,但在4小时采样期内,除给药后立即出现差异外,两组的血浆芬太尼浓度相似。这些结果表明,如果对芬太尼的反应存在与年龄相关的差异,可能的药代动力学解释是老年患者给药后体内芬太尼浓度较高。