The interindividual variability (IIV) with the log-normal distribution was allowed for parameters:

where θP is a typical value of parameter P, ηP denotes its individual realization, and ωP2 is the variance in the log-domain. Selection of IIV parameters for the final model started with variances for CL/FIM, Vp/FIM and increasing their number until either the estimation failed, precision of estimates were unacceptable, or goodness of fits plots were aberrant.

The observed drug plasma concentrations Cij were log-transformed and the constant residual error model was applied:

where tij is the jth observation time for the ith subject and σ2 is the variance of the residual error εi that was same for all subjects.

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