Kitts J B, Fisher D M, Canfell P C, Spellman M J, Caldwell J E, Heier T, Fahey M R, Miller R D
Department of Anesthesia, University of California, San Francisco 94143-0648.
Anesthesiology. 1990 Feb;72(2):272-5. doi: 10.1097/00000542-199002000-00011.
To evaluate the effect of aging on the distribution, clearance, and neuromuscular junction sensitivity to atracurium, the authors determined the pharmacokinetics and pharmacodynamics of atracurium in five healthy elderly subjects (74-76 yr) during halothane-nitrous oxide anesthesia and compared these values to those obtained previously in five healthy young adults (22-44 yr). A brief (6.0-13.0 min) infusion of atracurium was administered until twitch tension was suppressed by approximately 70%, and atracurium plasma concentration and twitch tension data were used to determine pharmacokinetic and pharmacodynamic parameters for each patient. Total clearance (Cltotal) was similar in elderly and young adults. However, clearance via the liver and/or kidney (Clorgan) was lower in elderly patients, whereas clearance due to Hofmann elimination and ester hydrolysis (Clnonorgan) was higher. Volume of distribution at steady state (Vss) was larger in elderly patients. The increase in Vss without an age-related increase in Cltotal resulted in a longer elimination half-life [21.8 (+)/- 3.3 vs. 15.7 (+)/- 2.5 min (mean (+)/- SD)] in elderly patients. The steady state plasma concentration of atracurium required to suppress twitch tension by 50% was similar in elderly and young adults. The authors conclude that the pharmacokinetics, but not the pharmacodynamics, of atracurium differ significantly between elderly and young adults. As a result, repeated doses will be required with similar frequency in young and elderly adults, but recovery from comparable levels of neuromuscular blockade may be slightly prolonged in elderly patients.
为评估衰老对阿曲库铵分布、清除及神经肌肉接头敏感性的影响，作者测定了5名健康老年受试者（74 - 76岁）在氟烷-氧化亚氮麻醉期间阿曲库铵的药代动力学和药效学，并将这些值与之前在5名健康年轻成年人（22 - 44岁）中获得的值进行比较。给予阿曲库铵短暂输注（6.0 - 13.0分钟），直至颤搐张力被抑制约70%，并使用阿曲库铵血浆浓度和颤搐张力数据来确定每位患者的药代动力学和药效学参数。老年和年轻成年人的总清除率（Cltotal）相似。然而，老年患者经肝脏和/或肾脏的清除率（Clorgan）较低，而霍夫曼消除和酯水解导致的清除率（Clnonorgan）较高。老年患者的稳态分布容积（Vss）更大。Vss增加而Cltotal未随年龄增加，导致老年患者的消除半衰期更长[21.8（±）/- 3.3对15.7（±）/- 2.5分钟（均值（±）标准差）]。抑制颤搐张力50%所需的阿曲库铵稳态血浆浓度在老年和年轻成年人中相似。作者得出结论，阿曲库铵的药代动力学在老年和年轻成年人之间有显著差异，但药效学无显著差异。因此，年轻和老年成年人需要以相似频率重复给药，但老年患者从相当程度的神经肌肉阻滞中恢复可能会稍有延长。
