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The comparative potency and pharmacokinetics of pancuronium and its metabolites in anesthetized man

RD Miller, S Agoston, LH Booij, UW Kersten, JF Crul and J Ham

To determine the potency of pancuronium and its metabolites, 3-OH-, 17- OH- and 3,17-OH-pancuronium, cumulative dose-response curves were determined in five 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, one equipotent dose of either pancuronium or one of its metabolites was given as an i.v. bolus. Onset time and duration of neuromuscular 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 four 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. We conclude that although pancuronium is more potent than its 3-OH, 17-OH and 3,17-OH metabolites, the pharmacokinetics of these three metabolites do not differ from each other and from that of pancuronium.

Volume 207, Issue 2, pp. 539-543, 11/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics.