IIV terms were included on the apparent total body clearance (CL/F), apparent volumes of distribution in the central and peripheral compartments (V1/F and V2/F,

respectively), and ka. IOV was included on Frel, D1, and ka. A proportional error model was used to describe the residual variability. The parameter estimates for the final population pharmacokinetic model are presented in table VIII. Table VIII GLPG0259 parameter estimates for the final population pharmacokinetic model The residual variability for the final model (15.0%) was low and showed that the final population pharmacokinetic model described the vast majority of the variability in the data. RAD001 ic50 The value of CL/F estimated for GLPG0259 was 79.3 L/h and was estimated with high precision (relative standard error [SE] 4.0%). The estimate of V1/F was 3030 L and was also precise (relative SE 4.4%). The values for CL/F and V1/F could be used to obtain the t1/2,λz for GLPG0259, which was calculated to be 26.5 hours. In general, all of the

parameters associated with the disposition of GLPG0259 were estimated GKT137831 molecular weight precisely (IIV around 20%). Parameters associated with absorption RO4929097 were less precisely estimated (IIV and IOV ranged between 20% and 75%), indicating that the majority of the overall variability in the pharmacokinetics of GLPG0259 was due to absorption. The value of ka at a dose of 50 mg was calculated to be 0.88/hour. The goodness-of-fit plots for the final population pharmacokinetic model of GLPG0259 are shown in figures 6 and 7. Fig. 6 Goodness-of-fit plots: observed data are plotted on the y-axes, and population predictions [graphs (a) and (b)] and individual model predictions [graphs (c) and (d)] are plotted on the x-axes. Graphs () and (c) are on a linear scale, and graphs (b) and (d) are on a logarithmic scale. The dashed datalines are identity lines, and the thick solid datalines are smoothes through the data.

The smooth lines lie very close to the identity lines, for both the population and individual predictions, indicating that the structural model describes the data well. IPRED = individual predictions; PRED = population predictions. Fig. 7 Goodness-of-fit plots: (a) conditional weighted residuals versus population predictions; (b) absolute Niclosamide individual weighted residuals versus individual predictions; (c) conditional weighted residuals versus time after dose; (d) conditional weighted residuals versus continuous time. The dashed datalines are zero lines, and the thick solid datalines are smoothes through the data. The lack of trends in graphs (), (c), and (d) again indicates that the structural model describes the data well. The lack of a trend in the smooth line in graph (b) shows that the proportional error model is appropriate for describing the residual error.