Fig. 5. (A ) Time course of predicted plasma concentration (Cp), predicted pharmacodynamic effect, and the corresponding values of V̇E50 (measured effect) in the subjects. (B ) Relation between effect-site concentration (from the pharmacokinetic–pharmacodynamic model) and the observed V̇E50 in the subjects. The dotted line is the sigmoidal function that predicts V̇E50 from the effect-site concentration.