Neuromuscular blockade and pharmacokinetic-pharmacodynamic modeling

ABSTRACT

A major goal in pharmacokinetic-pharmacodynamic (PK/PD) modeling of neuromuscular blockade (NMB) is to quantitatively estimate the dose-response relationship.Our PK/PD model consists of three submodelsPK, link kinetics, and PD.A virtual effect compartment in which the drug concentration is in equilibrium with the observed concentration is used to extract the kinetic component (keo) from the pharmacodynamic data alone.Parameters of this model are keo, Ce(50), and gamma.The underlying structural pharmacokinetics and pharmacodynamics for NMB have been well understood, and new novel PK/PD models have been substituted for the gold standard PK/PD model for NMB.The purpose of this review was to describe progress in the field of PK/PD modeling of NMB from the first model, a simultaneous PK/PD model developed by Sheiner et al in the 1970s, to some of the more complicated models.Specific PK/PD models, which accurately described the behaviors of rocuronium, mivacurium, atracurium, and cisatracurium, include the recirculatory model, the peripheral link model, the peripheral elimination model, and a nonparametric model for link kinetics.