Population parameters were originally estimated either by fitting the combined data from all the individuals, ignoring individual differences (the "naive pooled approach"), or by fitting each individual's data separately and combining individual parameter estimates to generate mean (population) parameters (the "two-stage approach").
For each step the explained percentage of the interindividual variability of a significant covariate was calculated according to (Draper and Smith, 1966): where n is the number of patients, P i is the individual model predicted PK parameter and p̄ is the mean population PK parameter, that is, both according to the basic PK model.
All mean population PK parameter estimates fell within the 95% CI of bootstrap resampling of 2,000 replicates simulated.
For humans, mean population PK parameters for sunitinib and its metabolite SU12662, estimated with a two-compartment model, were obtained.
Mean population pharmacokinetic parameters were; apparent clearance 15.9l h−1, apparent volume of distribution 85 l and absorption lag time 40 min.
We tested for significant differences in mean population genetic parameters (HO, FIS, and AR) among populations with distinct Bd disease dynamics.
Mean population pharmacokinetic parameters included an apparent clearance of 15.9 l h−1, apparent volume of distribution of 85 l and absorption lag time of 40 min with a large inter-individual variability associated with all parameters (coefficients of variation greater than 50%).
Individual level PK analyses require relatively dense data for each subject, whereas population level PK models allow simultaneous estimation of mean population PK parameters, as well as between subject variability (of biological origin) and residual unexplained variability (including other stochastic factors, e.g. assay variation) [9].
An arbitrary criterion for successful verification of the model was prediction of pregnancy-induced fold-changes in mean population PK parameters of the drug (i.e., AUC ratio (PP T3), Cmax ratio (PP T3), and Cmin ratio (PP T3)) between 80% and 125% of the observed value, i.e., 0.80≤pred/obs≤1.25.
Table 4 presents the comparative mean population amikacin pharmacokinetic parameters of Kuwaiti patients in contrast to other ethnic groups including Hispanic, Asian, and Caucasian subjects.
