*Vmax Maximum elimination rate for first order process, Km drug concentration that – – results in half Vmax The median (interquartile of the pyrazinamide AUC0-24 and Cmax were 418 mg.h/L and 34 (29-39) mg/L respectively. Ethambutol One percent of the observations were the LLOQ of 0.1 mg/L. These missing observations were imputed to half of the LLOQ value, Beal’s M5 method (4). Minor modifications to a published model in a similar cohort of patients (2) revealed that an absorption model with an estimated 5 transit compartments, followed by first order elimination from a 1-compartment model adequately described the data. FOCE with ε-η interaction was the estimation algorithm employed. Clearance and volume were allometrically scaled for bodyweight. WSV in the absorption mean transit time, clearance and volume was included in the final model. BSV in clearance was also incorporated although BSV in other model parameters could not be supported by the data. A combined additive and proportional error model was used to describe the residual unexplained variability. The final model parameter estimates and RSE from the NONMEM covariance step are shown in supplementary table 4. Table S4: Ethambutol population pharmacokinetic model parameter estimates
*Vmax – Maximum elimination rate for first order process, Km – drug concentration that results in half Vmax The median (interquartile of the pyrazinamide AUC0-24 and Cmax were 418 mg.h/L and 34 (29-39) mg/L respectively. Ethambutol One percent of the observations were the LLOQ of 0.1 mg/L. These missing observations were imputed to half of the LLOQ value, Beal’s M5 method (4). Minor modifications to a published model in a similar cohort of patients (2) revealed that an absorption model with an estimated 5 transit compartments, followed by first order elimination from a 1-compartment model adequately described the data. FOCE with ε-η interaction was the estimation algorithm employed. Clearance and volume were allometrically scaled for bodyweight. WSV in the absorption mean transit time, clearance and volume was included in the final model. BSV in clearance was also incorporated although BSV in other model parameters could not be supported by the data. A combined additive and proportional error model was used to describe the residual unexplained variability. The final model parameter estimates and RSE from the NONMEM covariance step are shown in supplementary table 4. Table S4: Ethambutol population pharmacokinetic model parameter estimates
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