Fourteen patients undergoing elective surgery were studied at two levels of gallamine dosage. Seven patients received a single bolus dose of 4 mg/kg, and the remainder received 6 mg/kg. The venous plasma concentration-time data from both groups were characterized in terms of a two-compartment open model. No significant differences in the various pharmacokinetic parameters were noted. However the distribution and clearance terms from these two patient groups were significantly higher than those obtained with a previous group of patients receiving lower (2 mg/kg) single and multiple doses. Assessment of neuromuscular twitch response showed that maximum blockade was attained in all patients within 5 min with the time to peak effect being dose dependent. Recovery from paralysis as assessed at 99, 95 and 90% paralysis indicated that the duration of action was similarly dose dependent. The concurrently measured plasma concentrations showed wide variation but were higher at more profound levels of paralysis. Arterial blood samples for 5 patients receiving the 4 mg/kg gallamine dose were taken simultaneously with the venous samples over the first sixty minutes. No significant arterio-venous differences in gallamine plasma concentration were noted at any time interval in all subjects.

Plasma concentrations of gallamine were determined in 6 patients undergoing anaesthesia for elective surgery receiving a single intravenous bolus dose of 2 mg/kg and in a further 11 patients requiring additional doses (0.5 to 2 mg/kg) of the relaxant. The two-compartment open model was found to characterize adequately both the single and multiple dose data. No significant differences were noted when the model-independent pharmacokinetic parameters between the two groups of patients were compared with the exception of the distribution phase half-life (t1/2 alpha) (6.70 min single vs 9.19 min multiple p less than 0.05). Mean values for the pooled data for the half-life (t1/2 beta), plasma clearance (Clp) and volume of distribution (Vd beta) were 134.58 min, 1.20 ml/min/kg and 225.28 ml/kg respectively. Evoked twitch response was monitored in each patient to assess the degree of neuromuscular blockade. In only one patient was the bolus dose sufficient to produce complete (100%) blockade, thus the degree of maximal response varied between 78 to 100% and took some 3 to 10 minutes after dose administration. The concurrently measured gallamine plasma concentrations ranged from 9.30 to 19.20 micrograms/ml. Linear regression of the offset data (20 to 80% paralysis) in 10 patients revealed a recovery rate of 0.35 to 1.33%/min. For 5 patients where offset data was available over the entire range of response (0 to 100%) the calculated mean effective plasma concentrations for gallamine at 50 and 95% paralysis (ECp50, ECp95) were found to vary between 3.43 to 10.28 micrograms/ml, and 5.66 to 23.37 micrograms/ml respectively.

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.