Sitar D S, Duke P C, Benthuysen J L, Sanford T J, Smith N T
Geriatric Clinical Pharmacology Unit, University of Manitoba, Winnipeg.
Can J Anaesth. 1989 Mar;36(2):149-54. doi: 10.1007/BF03011438.
We studied the pharmacokinetic disposition of alfentanil in 20 volunteers and in 15 surgical patients 20-72 years old. Pharmacokinetic disposition was first order and was well described by a two-compartment open model. Central-compartment volume of distribution was 0.131 +/- 0.087 L.kg-1 (mean +/- SD) in young healthy volunteers and decreased modestly with increasing age (r = -0.32, P less than 0.05). However, apparent volume of distribution at steady-state, 0.404 +/- 0.205 L.kg-1 for the whole study cohort, was not age-related. Plasma clearance of alfentanil in young healthy subjects, 9.3 +/- 6.3 ml.kg-1.min-1, also showed an inverse relationship with age (r = -0.54, P less than 0.001), and was not affected by surgical stress in subjects older than 60 years. Cigarette smoking and sex of the subjects did not contribute to interindividual differences in the kinetic disposition of this drug. Our finding that interindividual differences in disposition of alfentanil were the least in older subjects suggests that its pharmacological effects related to pharmacokinetic disposition should be most predictable in the elderly.
我们研究了阿芬太尼在20名志愿者和15名年龄在20至72岁之间的外科手术患者体内的药代动力学情况。药代动力学呈一级过程，可用二室开放模型很好地描述。年轻健康志愿者的中央室分布容积为0.131±0.087L·kg⁻¹（均值±标准差），并随年龄增长略有下降（r = -0.32，P<0.05）。然而，整个研究队列的稳态分布容积为0.404±0.205L·kg⁻¹，与年龄无关。年轻健康受试者的阿芬太尼血浆清除率为9.3±6.3ml·kg⁻¹·min⁻¹，也与年龄呈负相关（r = -0.54，P<0.001），且在60岁以上的受试者中不受手术应激的影响。受试者的吸烟情况和性别对该药物动力学分布的个体间差异没有影响。我们的研究发现，阿芬太尼分布的个体间差异在老年受试者中最小，这表明其与药代动力学分布相关的药理作用在老年人中最具可预测性。
