An analytical pharmacodynamic model for nondepolarizing neuromuscular blocking agents

A pharmacodynamic model for nondepolarizing neuromuscular blocking agents (NMBA) is developed and tested with different sets of data (NMBA plasma concentration and time evolution of muscular paralysis). This model takes into account the binding of NMBA to the cholinergic motor endplate receptors and thus permits estimation of the apparent equilibrium constant of the NMBA-receptor exchange. The parameters defining the relationship between relative postsynaptic receptor occupation and muscular paralysis can also be determined. The simulated muscular paralysis time curves, calculated for various modes of NMBA administration (loading injection and multiple injections or continuous infusion) are comparable to those observed clinically. As compared to previous NMBA pharmacodynamic models, the model presented in this study utilizes and describes all the main steps between changes in the plasma NMBA concentration and the observed response: pharmacokinetics, ligand-receptor exchanges, and receptor occupation-effect relationship. This model illustrates a general methodology for the study of pharmacokinetic and pharmacodynamic problems.