PHARMACOKINETICS AND PHARMACODYNAMICS OF ATRACURIUM IN THE ELDERLY

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 pharmacokinetics and pharmacodynamic parameters for each patient. Total clearance (Cl(total)) was similar in elderly and young adults. However, clearance via the liver and/or kidney (Cl(organ)) was lower in elderly patients, whereas clearance due to Hofmann elimination and ester hydrolysis (Cl(nonorgan)) was higher. Volume of distribution at steady state (V(ss)) was larger in elderly patients. The increase in V(ss) without an age-related increase in Cl(total) 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.