TABLE 4

F tests comparing various PBPK models (A–H) with different combinations of linear and nonlinear elimination pathways

ModelDescriptiondf a SSWR b F Score c Critical F Value d Significance e AIC Value f
ANo nonlinear pathway189653NA g NANA3297
BNonlinear Embedded Image only188837−41.3 Embedded Image No3370
CNonlinear Embedded Image only188808−36.0 Embedded Image No3322
DNonlinear Embedded Image only188695−11.4 Embedded Image No3293
ENonlinear Embedded Image and Embedded Image 187287119 Embedded Image Yes3244
FNonlinear Embedded Image , Embedded Image , and Embedded Image 186250100 Embedded Image Yes3235
GNonlinear Embedded Image , Embedded Image , and Embedded Image 186234111 Embedded Image Yes3225
HNonlinear Embedded Image , Embedded Image , Embedded Image , and Embedded Image 18571.4377 Embedded Image Yes3214
  • a The df is the number of data points (n = 198) used in the model minus the number of parameters being fitted.

  • b The SSWR was calculated using Embedded Image . The total SSWR for verapamil, preformed, and formed norverapamil data in perfusate, bile, and liver compartments was calculated.

  • c The F score was calculated using Embedded Image , where df j > df i .

  • d The critical F value was obtained from the F table with a numerator of df j –df i and denominator of df i .

  • e The significance level was α = 0.05; Models E–H showed significant improvement in the goodness-of-fit compared with Model A.

  • f The AIC, a measurement of the goodness-of-fit, is calculated as Embedded Image , where k is the number of parameters fitted in the model, and likelihood is the maximized value of the likelihood function.

  • g Not available