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 only188837−41.3 No3370
CNonlinear only188808−36.0 No3322
DNonlinear only188695−11.4 No3293
ENonlinear and 187287119 Yes3244
FNonlinear , , and 186250100 Yes3235
GNonlinear , , and 186234111 Yes3225
HNonlinear , , , and 18571.4377 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 . 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 , 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 , where k is the number of parameters fitted in the model, and likelihood is the maximized value of the likelihood function.

• g Not available