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

Abstract

Twenty-eight elderly patients (>75 years old) and 43 younger patients (25 to 60 years 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 to 100 μg/kg) were compared in the two groups. The plasma concentration-response relationship was established during recovery from paralysis. The pharmacokinetics of pancuronium 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 per cent paralysis averaged 39 ± 10 and 44 ± 12 μg/kg in control subjects and elderly patients, respectively. The plasma concentrations corresponding to a fixed degree of neuromuscular blockade were similar between the two groups. The time for recovery of the twitch tension to 25 per cent 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 per cent of the control value also was prolonged from 39 ± 13 to 62 ± 30 min in the elderly patients. The plasma clearance was decreased by 35 per cent 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. It is concluded that pancuronium exerts a prolonged effect in elderly patients because of delayed elimination; the pharmacodynamics of pancuronium are not altered by aging.