Fig. 1. A schematic summary of the infusion scheme. During each of the three study periods, the primary drug is administered in a stepwise fashion (  solid black line ), whereas in the second and third study periods, the second drug (  gray filled area ) is held at a constant predicted effect site concentration or measured alveolar concentration. In between each study period, there is a washout phase, during which the primary and secondary drugs are allowed to decay to predicted concentrations below that of the subsequent target concentration pair.