Fig. 3.

Distributions of parameter estimates via bootstrapping (model 5). The red line indicates the original estimates from model 5, the vertical black line indicates the median of 1000 bootstrapped samples. The values of SIGMA.1.1 and VMAXSTUDY1102 were not estimated. The effect of study 1102 on V_max was evaluated by pooling with the pharmacokinetic data from study 1155. K_dec was estimated by division with 1000 (e.g., the value of 3 in the K_dec plot corresponds to estimated K_dec of 0.003 1/day). CL clearance, IIV interindividual variability, K_dec first-order rate constant for decrease in V_max, K_m concentration to achieve half of V_max, prop.err proportional error, Q intercompartmental clearance, V_c volume of distribution in the central compartment, V_max maximum velocity of the saturable clearance process V_p volume of distribution in the peripheral compartment, WT body weight