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).