COMPARATIVE POTENCY AND PHARMACOKINETICS OF PANCURONIUM AND ITS METABOLITES IN ANESTHETIZED MAN

Abstract

To determine the potency of pancuronium and its metabolities, 3-OH-, 17-OH- and 3,17-OH-pancuronium, cumulative dose-response curves were determined in 5 anesthetized patients with each drug. Pancuronium (ED50 = 0.041 mg/kg) was 2 times more potent than 3-OH-pancuronium (ED50 = 0.082 mg/kg), 50 times more potent than 17-OH-pancuronium (ED50 = 2.0 mg/kg) and 54 times more potent than 3,17-OH-pancuronium (ED50 = 2.15 mg/kg). In 21 other patients, 1 equipotent dose of either pancuronium or one of its metabolites was given as an i.v. bolus. Onset time and duration of neuromusculcar blockade from 3-OH- and 3,17-OH-pancuronium did not differ significantly from that of pancuronium; 17-OH-pancuronium had a shorter duration of action than did pancuronium. Although pancuronium tended to have a slightly longer elimination half-life, the pharmacokinetics of the 4 drugs did not differ significantly. The elimination half-lifes were 110, 68, 73 and 71 min for pancuronium and its 3-OH, 17-OH and 3,17-OH derivatives, respectively. Although pancuronium is more potent than its 3-OH, 17-OH and 3,7-OH metabolites, the pharmacokinetics of these 3 metabolities do not differ from each other and from that of pancuronium.