Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC45) and pancuronium in anesthetized humans

Abstract

The pharmacokinetics and pharmacodynamics of vecuronium (25-50 μg/kg) and pancuronium (25-50 μg/kg) were determined in nine ASA class I or II patients anesthetized with nitrous oxide and halothane. Force of the thumb adduction in response to supramaximal stimulation of the ulnar nerve was quantified and recorded. Serum concentrations of the muscle relaxants were determined for eight hours after their administration using a mass spectrometry assay. Data were analyzed by nonlinear regression and fit to a three-compartment pharmacokinetic model and a four-compartment pharmacodynamic model. Vecuronium had a more rapid clearance (5.2 ± 0.7 ml.kg-1.min-1.min-1; mean ± SD) and a shorter elimination half-life (71 ± 20 min) as compared with pancuronium (1.8 ± 0.4 ml.kg-1.min-1; 140 ± 25 min). No other pharmacokinetic differences were found between the drugs. Pharmacodynamic analysis showed that the plasma concentration at steady state which produced a 50% neuromuscular blockade (Cp(ss) 50) was similar for vecuronium and pancuronium. The authors conclude that the drugs are equivalent in their onset and potency; however, the more rapid clearance and shorter elimination half-life for vecuronium provides a kinetic basis for its shorter duration of neuromuscular blockade as compared with pancuronium.