Relationship Between Gallamine Plasma Concentration and Neuromuscular Paralysis in Surgical Patients

Abstract

The pharmacodynamics of the neuromuscular blocking drug gallamine were investigated in 10 surgical patients using a constant-rate infusion regimen, and results are compared to those for d-tubocurarine (dTc). Gallamine effect (paralysis)-time data gathered during and following the infusion were fitted to a pharmacodynamic effect model, while paralysis-plasma concentration data gathered during (onset) and following (offset) the infusion were fitted separately to a nonlinear form of the Hill equation. The effect model was most appropriate in characterizing the combined (on and off infusion) effect data. While there was also an excellent characterization of onset and offset data with the Hill equation, the two effect-concentration curves were not superimposable. The mean (+/- S.D.) plasma concentration of gallamine at 50 per cent paralysis during onset of action (Cp50(onset) 8.0 +/- 1.8 micrograms/ml) or that predicted to exist at steady state using the effect model (Cp50(ss) 5.4 +/- 1.4 micrograms/ml). Cp50(offset) and Cp50(ss) did not differ significantly, and there was no significant difference in the power factor (lambda) estimates for the various model fits. Comparison of the pharmacodynamic parameters for gallamine and dTc using the effect model revealed no significant differences in keo, t1/2(keo), and lambda estimates. However, Cp50(ss) for gallamine (5.4 +/- 1.4 micrograms/ml) was nine times higher than that for dTc (0.61 +/- 0.15 micrograms/ml) in absolute terms and seven times higher when compared on a molar basis.

Muscle Distribution of the Neuromuscular Blocker gallamine Using Microdialysis

“…This implies that gallamine distribution is more extensive in rats. Indeed, this is consistent with literature values of volume of distribution of gallamine in humans of ∼0.3 L/kg11,23 compared with 0.6 L/kg in rats found in this study. However, the value of volume of distribution may not accurately reflect the precise distribution of gallamine into rat MIF.…”

“…This drug has been chosen as a model compound in our studies to investigate the pharmacokinetics and pharmacodynamics of the neuromuscular blockers using continuous sampling from muscle tissue by microdialysis. Gallamine has negligible plasma protein binding and is not metabolized 7,11–13. It acts at peripheral sites with an effective concentration above 1 μg/mL which permits its assay in the small sample volumes typically generated using microdialysis 7,11.…”

“…Gallamine has negligible plasma protein binding and is not metabolized 7,11–13. It acts at peripheral sites with an effective concentration above 1 μg/mL which permits its assay in the small sample volumes typically generated using microdialysis 7,11. Furthermore, gallamine produces a pharmacodynamic effect (muscle paralysis) that is easily quantified.…”

Vecuronium Pharmacokinetic-Pharmacodynamic Modelling With and Without a Receptor Concentration in the Effect Compartment in Anaesthetised Patients

“…For pancuronium and gallamine, the percentage of paralysis was plotted against plasma concentrations (Evans et al 1984;Ramzan et al 1983) or the logarithm of plasma concentrations (Shanks et al 1979). The only comparison between onset and recovery phases was based on plasma rather than effect site concentrations, and all experiments used short infusions.…”