Abstract
BackgroundThe study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants.MethodsThe molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment.ResultsThe simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities.ConclusionAn experimental design to estimate the volume of the effect compartment is suggested.
Highlights
The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants
Receptor concentration in the effect compartment is the ratio of this amount and the volume assigned to the effect compartment
The target amounts of the muscle relaxant in plasma and those estimated in compartment1 as well as the amounts in the small and the large effect compartments are graphically presented in the upper panel of Figure 1
Summary
The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. In the majority of the pharmacokinetic-pharmacodynamic (PK-PD) models proposed to simulate neuromuscular block (NMB) [1,2,3], the volume of the effect compartment is postulated to be negligibly small or the compartment is postulated to contain a negligibly small amount of the muscle relaxant. Theoretical Biology and Medical Modelling 2005, 2:41 http://www.tbiomed.com/content/2/1/41 relaxants to the receptors. These investigators suggested that the receptor concentration in the effect compartment is 2.8·10-7 M, but the volume of the effect compartment was assumed to be negligibly small. Given a fixed amount of postsynaptic receptors, a finite receptor concentration is not compatible with a negligibly small volume of the effect compartment
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