PMC

Visual predictive checks. (a–d) Unbound lopinavir (LPV), (e–h) total LPV, (i–l) unbound ritonavir (RTV), and (m–p) total RTV. The colored lines represent the prediction percentiles: red solid lines for medians and blue dashed lines for 5^th and 95^th percentiles of prediction. The black lines represent the observation percentiles: solid lines for medians and dot‐dash lines for 5^th and 95^th percentiles of observation. The black dots represent the observed data. The colored shaded areas are the 95% confidence intervals (CI) of the prediction percentiles: red shading for 50^th percentiles and blue shading for 5^th and 95^th percentiles.

Diagnostic plots. (a–d) Unbound lopinavir (LPV), (e–h) total LPV, (i–l) unbound ritonavir (RTV), and (m–p) total RTV. From the left to the right are observation (DV) vs. individual prediction (IPRED), observation vs. population prediction (PRED), conditional weighted residual (CWRES) vs. time and conditional weighted residual vs. population prediction plots. The solid lines in the left two columns represent the lines of unity. The blue dashed lines are loess regression lines. The red dashed lines in right columns are loess regression lines of the absolute residual values. Values from different visits are denoted in different shapes.

Schematic illustrations of the pharmacokinetic model structure for (a) lopinavir and (b) ritonavir. X₀, oral dose; X_a, amount of drug in the absorption compartment; k_a, first‐order absorption rate constant; T_lag, absorption lag time; f_u, unbound fraction; C_u, unbound concentration; C, total concentration; V_u/F, apparent volume of distribution of unbound drug; V/F, volume of distribution of total drug; CL_u/F, apparent unbound drug clearance or intrinsic clearance; F, bioavailability; LPV, lopinavir; RTV, ritonavir. * and † denote the interindividual variability and interoccasion variability on the parameters in the final model, respectively.