Clinical pharmacokinetics of the non-depolarising muscle relaxants

Muscle relaxants are of great benefit to the anaesthetist as adjuncts to anaesthesia. These drugs are used to facilitate endotracheal intubation and to reduce muscle tone during surgery, and may also find application in assisting ventilator care in the intensive care situation. The pharmacological effect of the relaxants may be readily assessed by the anaesthetist by means of a variety of techniques to quantify muscular activity in response to electrical stimulation. A number of factors may modify the effects of the muscle relaxants including anaesthetic agents, hypothermia, patient age and disease status and a variety of drugs. The disposition kinetics of the muscle relaxants have been well characterised although information on protein binding and placental transfer is somewhat scanty. A common characteristic of their pharmacokinetics is multicompartmental behaviour. Clearance of the relaxants ranges from total elimination by the kidneys (gallamine) to substantial hepatic clearance (fazadinium), and thus their clearance may be adversely affected by renal or hepatic disease. Dosage regimens have been designed using knowledge of the disposition kinetics of the relaxants to provide for continuous adequate relaxation during prolonged surgical procedures. With the use of sophisticated pharmacokinetic and pharmacodynamic models good relationships have been demonstrated between plasma concentrations of the relaxants throughout the entire range of relaxant response.