The pharmacology of
3-desacetylvecuronium, the principal metabolite of
vecuronium, was investigated. We studied 12 healthy volunteers, each on two occasions. First they received
3-desacetylvecuronium alone and then, on a later occasion,
vecuronium. Six subjects received a large dose of each
drug (pharmacokinetic study), the remaining six received a small dose (pharmacodynamic study).
Drug concentrations in plasma and urine were measured using capillary gas chromatography. Neuromuscular block was assessed by measuring force of contraction of the adductor pollicis.
Drug plasma concentration vs. time and
neuromuscular effect data were analyzed by nonlinear mixed-effects modeling.
3-Desacetylvecuronium, compared with
vecuronium (median, range in parentheses), had a smaller plasma clearance, 3.51 (2.11-6.57) vs. 5.39 (5.04-7.19) ml.kg-1.min-1; a larger steady-state distribution volume, 254 (215-410) vs. 152 (111-170) ml.kg-1; a longer terminal elimination half-life 116 (44-672) vs. 34 (25-61) min and a longer mean residence time, 67 (42-145) vs. 26 (18-32) min (P < .05). Renal clearances of
3-desacetylvecuronium and
vecuronium were 0.85 (0.15-1.24) and 0.58 (0.16-0.66) ml.kg-1.min-1, respectively (P < .05). Conversion to
3-desacetylvecuronium accounted for 12% of
vecuronium's clearance. Concentrations of
3-desacetylvecuronium and
vecuronium that produced 50% neuromuscular block were 123 (109-154) and 102 (71-123) ng.ml-1, respectively (P < .05).
3-Desacetylvecuronium is a potent neuromuscular blocking
drug and may be responsible for episodes of prolonged
paralysis after long-term administration of
vecuronium to patients in intensive care units.