Pharmacokinetics and Pharmacodynamics of Doxacurium in Young and Elderly Patients During Isoflurane Anesthesia

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Abstract
Preliminary disposition studies of the investigational, long-acting muscle relaxant doxacurium chloride (Nuromax) have demonstrated dual elimination by renal and hepatobiliary pathways, as well as slow hydrolysis by plasma cholinesterase. The present study compares the kinetics and dynamics of doxacurium in eight ASA physical status I or II elderly patients (67-72 yr of age) and eight ASA I or II young patients (22-49 yr of age). After institutionally approved written informed consent, kinetic and dynamic measurements were made after a 25 .mu.g/kg bolus injection of doxacurium during 1.25 MAC nitrous oxide/oxygen/isoflurane anesthesia. Maximum twitch depression was similar in older patients (96.4% .+-. 1.3%) to that in the young patients (96.6% .+-. 1.8%). The time to achieve this level of block was significantly longer in the elderly than in the young (11.2 .+-. 1.1 min versus 7.7 .+-. 1.0 min, respectively). Recovery times to twitch heights of 5% and 25% of control tended to be prolonged and were more variable in the elderly (82.6 .+-. 17.2 and 97.1 .+-. 20.1 min, respectively) than in the young (54.8 .+-. 9 and 67.5 .+-. 8.2 min, respectively). Elimination half-life (96 .+-. 20 min) and clearance (2.47 .+-. 0.69 mL.cntdot.kg-1.cntdot.min-1) in the elderly patients were not statistically different from values found in the younger group. Volume of distribution at steady state in the elderly (220 .+-. 80.2 mL/kg) was significantly larger than in the young (150 .+-. 40.0 mL/kg). Renal excretion of unchanged drug was an important route of elimination, accounting for 24% of the dose in the elderly and 31% in the young. The observed pharmacokinetic and dynamic profile suggests that doxacurium may be given in a similar dosage regimen to both young and elderly patients.