Pharmacokinetics, Pharmacodynamics, and Dose–Response Relationships of Pancuronium in Control and Elderly Subjects

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Abstract
Twenty-eight elderly (> 75 yr old) and 43 younger patients (25-60 yr old) were studied to evaluate the effect of aging on the pharmacokinetics and pharmacodynamics of pancuronium. The pancuronium dose-response relationship and the duration of neuromuscular blockade after the administration of a single dose (70-100 .mu.g/kg) were compared in the 2 groups. The plasma concentration-response relationship was established during recovery from paralysis. Pancuronium pharmacokinetics were characterized after a single bolus dose by measuring plasma and urine concentrations of pancuronium fluorimetrically. The dose-response and plasma concentration-response relationships in elderly patients were comparable to that of the control group. The dose that caused 50% paralysis averaged 39 .+-. 10 and 44 .+-. 12 .mu.g/kg in control subjects and elderly patients, respectively. The plasma concentrations corresponding to a fixed degree of neuromuscular blockade were similar between the 2 groups. The time for recovery of the twitch tension to 25% of the control value was prolonged from 44 .+-. 10 to 73 .+-. 22 min in the elderly patients. The recovery rate of the twitch from 25 to 75% of the control value was also prolonged from 39 .+-. 13 to 62 .+-. 30 min in the elderly patients. The plasma clearance was decreased by 35% in the elderly patients and caused a prolongation of the elimination half-life to 201 min as compared with 107 min in the younger adults. Urinary excretion of pancuronium was delayed in the elderly patients. Evidently pancuronium exerts a prolonged effect in elderly patients because of delayed elimination; the pharmacodynamics of pancuronium are not altered by aging.