Pharmacodynamic and Pharmacokinetic Study on the Neuromuscular Blocking Action of Rapacuronium: a Comparison with Other Muscle Relaxants

Abstract

Background:We evaluated the pharmacodynamic and pharmacokinetic properties of rapacuronium, a new non-depolarizing muscle relaxant.Methods: The EC50 and EC95 values of rapacuronium, vecuronium, and rocuronium were determined on rat hemidiaphragm, and reversal effects were determined using edrophonium or pyridostigmine. In 57 healthy adults, neuromuscular transmission was monitored at the adductor pollicis. Patients received a single dose of succinylcholine (1.0 mg/kg), rapacuronium (1.5 mg/kg), rocuronium (0.6 mg/kg), or mivacurium (0.16 mg/kg). Onset time, clinical duration, recovery index (RI), total duration (TD), train of four (TOF) ratio at over 95% recovery of control first twitch height, cardiovascular effect, and intubation scores were measured.Results: By in vitro study, the EC50 and EC95 of rapacuronium were 4 to 10 fold larger than those of vecuronium and rocuronium, and by clinical study, the onset time of rapacuronium was similar to those of succinylcholine. The clinical duration of rapacuronium was not different from those of succinylcholine and mivacurium. RI and TD of rapacuronium (9.6 ± 3.5 min and 30.9 ± 10.7 min) were longer than those of succinylcholine (3.5 ± 1.1 min and 18.1 ± 4.4 min) and mivacurium (6.5 ± 0.9 min and 23.0 ± 4.4 min) for spontaneous recovery, but not different during reversal by pyridostigmine (5.0μg/kg). The TOF ratio was increased after pyridostigmine than during spontaneous recovery. Intubation conditions of rapacuronium were similar to those of succinylcholine. Heart rates were significantly increased (15% of control) within 2 min, but not mean arterial pressure after rapacuronium was administration.Conclusions: Rapacuronium can be considered a valid alternative to succinylcholine and had no observed cardiovascular effect.