Pharmacokinetic studies in man with gallamine triethiodide

Abstract

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.

Gallamine disposition in surgical patients with chronic renal failure.

“…As a previous study conducted with an identical dosage of gallamine in normal surgical patients had demonstrated a significant preference for the biexponential model, the plasma concentration -time data for each patient receiving a single dose of relaxant was fitted to a biexponential macroparameter equation interpreted as a two-compartment open mammillary model (Ramzan et al, 1980a). With patient 8, who needed multiple doses of gallamine, the plasma level-time data was similarly fitted to a biexponential microparameter equation as reported previously (Ramzan et al, 1980a).…”

“…Clinical details for the patients are shown in Table 1. The normal patients (n = 17) were those undergoing routine general anaesthesia for elective surgery, and were as described in a previous report (Ramzan, Triggs & Shanks, 1980a). Half the group (patients 4, 6, 7 and 8) were given an intramuscular injection of a narcotic (either pethidine of papaveretum) about one hour preoperatively while the remainder were unpremedicated.…”

“…Neuromuscular function was assessed in all patients receiving gallamine. The intensity of paralysis was derived from the depression of the amplitude of the evoked compound muscle action potentials (EMG) using a method described elsewhere (Ramzan et al, 1980a). In brief, this involved single supramaximal stimuli applied to the ulnar nerve every 10 s, with observation and recording of the EMG from the muscles of the first interspace of the hand.…”

“…In the normal patient group, six patients received a single 2 mg/kg bolus intravenous dose while eleven patients received the same (2 mg/kg) initial dose followed by additional doses ranging from 0.5 to 2mg/kg as described previously (Ramzan et al, 1980a).…”

“…The blood samples were centrifuged and the plasma separated and stored at -20°C until assayed. Total gallamine plasma concentrations were determined by modification of the spectrofluorimetric procedure of Kersten, Meijer & Agoston (1973) for pancuronium as modified for gallamine by Ramzan et al (1980a).…”