Population pharmacokinetic analysis
LogThe principal structure of the pharmacokinetic modeling was based on our previous published population of PK models (Inter-individual variability as well as correlations between IIV terms was then evaluated for each parameter. The IIV was exponentially modeled for all parameters. Given the wide range of participant sizes, the most appropriate measure for allometric scaling (affecting volume and clearance terms) was selected from WT, fat free mass (FFM), ideal body weight (IBW), ABW, and a more complex model based on FFM with an additional parameter estimating the relative contribution of fat weight (WT-FFM) on each PK parameter (The model evaluation started with the inspection of goodness-of-fit plots including observed versus individual- and population-predicted values, and time versus CWRES. Bootstrapping was performed using Perl-speaks-NONMEM (PSN) with 1,000 samples to obtain 95% empirical confidence intervals for model parameters. Simulation-based model evaluation utilized prediction-corrected visual predictive checks using 1,000 data sets simulated from the final models. To assess the predictive performance of the model and to evaluate any major bias, the observed 10th, 50th, and 90th percentiles and the fraction of samples below the limit of quantification data observed were plotted with their respective simulated 90% 