FIG. 10

Modification of the kinetic–dynamic model to incorporate an effect-site, presumed to correspond to the site of pharmacologic activity. The first-order rate constant for drug exit from the effect-site (KEO) is effectively the rate constant determining the time necessary for drug equilibration between plasma and effect-site. Kinetic–dynamic linkage models are then applied to hypothetical effect-site concentrations rather than plasma concentrations.

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published 2000