Vecuronium

Vecuronium (vecuronium bromide) is a non-depolarising neuromuscular blocking agent, chemically designated as the aminosteroid 1-(3α, 17β-diacetoxy-2β-piperidino-5α-androstan-16β-yl)-1 methylpiperidinium bromide.

Vecuronium blocks the transmission process between the motor nerve-ending and striated muscle by binding competitively with acetylcholine to the nicotinic receptors located in the motor end-plate region of striated muscle.

Unlike depolarising neuromuscular blocking agents, such as suxamethonium, vecuronium does not cause muscle fasciculations.

Pharmacodynamic effects

Within the clinical dosage range, vecuronium does not block the sympathetic nicotininic receptors, and thus exerts no ganglion blocking activity. In addition, in this dose range vecuronium does not block the parasympathetic muscarinic receptors, and thus exerts no vagolytic activity.

Tracheal intubation

Within 90 to 120 seconds following intravenous administration of a dose of 80 to 100 micrograms vecuronium bromide per kg body weight, good to excellent conditions for endotracheal intubation occur and within 3 to 4 minutes following administration of these dosages, general muscle paralysis adequate for any type of surgery is established. The duration of action to 25% recovery of control twitch height (clinical duration) with this dose is 24 to 60 minutes. The time to 95% recovery of control twitch height following this dose is approximately 60 to 80 minutes. With higher dosages of vecuronium, onset time to maximal block is shortened and duration of action is prolonged.

Continuous intravenous infusion

When vecuronium is administered by continuous intravenous infusion, a steady state neuromuscular block of 90% can be maintained at a constant rate of drug delivery and without clinically significant prolongation of the recovery time from neuromuscular block at termination of the infusion.

Vecuronium has no cumulative effects if maintenance doses are administered at 25% recovery of control twitch height. Several maintenance doses can therefore be given in succession.

These properties allow the use of vecuronium in short, medium and long lasting surgical procedures.

Reversal of neuromuscular block

Administration of acetylcholinesterase inhibitors, such as neostigmine, pyridostigmine or edrophonium, antagonises the action of vecuronium.

Distribution

After intravenous administration of 100–150 micrograms/kg vecuronium, the distribution half-life of vecuronium amounts to 1.2-1.4 minutes.

Vecuronium is mainly distributed in the extracellular fluid compartment. At steady state, the volume of distribution is 0.18-0.51 l.kg^-1 in adult patients.

The plasma clearance of vecuronium amounts to 3.0-6.4 ml.kg^-1.min^-1 and its plasma elimination half-life is 36-117 minutes.

Biotransformation

The extent of metabolism of vecuronium is relatively low. In humans, a 3-hydroxy derivative having approximately 50% less neuromuscular blocking potency than vecuronium is formed in the liver. In patients not suffering from renal or hepatic failure, the plasma concentration of this derivative is below detection limit, and does not contribute to the neuromuscular block occurring after administration of vecuronium.

Elimination

Biliary excretion is the main elimination route. It is estimated that within 24 hours after intravenous administration of vecuronium, 40 to 60% of the dose administered is excreted into the bile as monoquaternary compounds. Approximately 95% of these monoquaternary compounds is unchanged vecuronium and less than 5% is 3-hydroxy vecuronium. Prolonged duration of action has been observed in patients with liver disease and/or biliary tract disease, probably as a result of decreased clearance leading to an increased elimination half-life.

Renal elimination is relatively low. The amount of monoquaternary compounds excreted in the urine collected by intravesical catheter for 24 hours following vecuronium administration is 20-30% of the dose administered. In patients with renal failure, the duration of action may be prolonged. This is probably the result of an increased sensitivity to vecuronium, but it could also be the result of a reduced plasma clearance.

Paediatric patients

There are limited pharmacokinetic data for vecuronium in the paediatric population. After intravenous administration, vecuronium plasma clearance is similar across neonates, infants and children (2.8-9.0 ml.kg^-1.min^-1) and not different from the clearance in adults. Volume of distribution at steady state (Vdss) in infants is similar to the one in adult patients (0.29-0.43 l/kg), whereas it is slightly smaller in children (0.13-0.32 l/kg).

Vecuronium showed no genotoxic, embryotoxic or teratogenic potential. Single and repeated dose toxicity studies in rats, dogs and cats revealed no special hazard for humans.