FIGURE 4.

Approximate profile likelihood of the composite parameters fbile + FaFg of the PBPK model for DDI of pitavastatin and rifampicin ¹¹ (Example 1). (a) Post hoc reparameterization, where the CGNM computation that estimated fbile and FaFg as separate parameters, and then when drawing approximate profile likelihood, reparameterized in post hoc manner (hence no additional model evaluation and took 0.5 s to draw this plot). (b) Approximate profile likelihood drawn based on the CGNM computation of the reparameterized model where fbile + FaFg is one of the unknown parameters (3.9 min). CGNM, Cluster Gauss‐Newton method; DDI, drug‐drug interaction; PBPK, physiologically‐based pharmacokinetic.