Goodness-of-fit and model evaluation
To describe the adequacy of the final population pharmacokinetic model, goodness-of-fit plots including observations versus population predictions, observations versus individual predictions, conditional weighted residuals (CWRES) versus population predictions, CWRES versus time were assessed. To evaluate the stability of final pharmacokinetic model, a bootstrap resampling procedure was performed. A total of 1000 bootstrap datasets were generated by random sampling with replacement and the pharmacokinetic parameters were re-estimated using the final population model. The median parameter value and their 95% confidence intervals (95% CIs) from bootstrap estimates were compared with the estimates of the final model. In addition, a visual predictive check (VPC) was used to assess the predictive ability of the final model. A total of 1000 simulations of the final population pharmacokinetic model were performed. The VPC graphically showed the observations and different percentiles of simulated concentrations (5th, median, and 95th percentiles).