Optimal experimental design can be used for optimizing new pharmacokinetic (PK)-pharmacodynamic (PD) studies to increase the parameter precision. Several methods for optimizing non-linear mixed effect models has been proposed previously but the impact of optimizing other continuous design parameters, e.g. the dose, has not been investigated to a large extent. Moreover, the optimization method (sequential or simultaneous) for optimizing several continuous design parameters can have an impact on the optimal design. In the sequential approach the time and dose where optimized in sequence and in the simultaneous approach the dose and time points where optimized at the same time. To investigate the sequential approach and the simultaneous approach; three different PK-PD models where considered. In most of the cases the optimization method did change the optimal design and furthermore the precision was improved with the simultaneous approach.