TABLE 4.

Empirical scaling factors used for prediction of K_p values and in vitro hepatic and renal CL_int data determined by optimization of the PBPK model using simultaneous fitting of in vivo concentration-time data from intact and anhepatic patients

Parameter	Initial Parameter Estimate	Model Fitted Parameter Estimatea	Model Fitted Scalara	CV% for Fitted Scalara
Kpb	—	—	0.54	9.5
Renal CLint,UGT (l/h per gram tissue)	0.786c	13.6	17.3	39
Hepatic CLint (l/h per gram tissue)d	1.57c	14.5	9.21	59

CV, coefficient of variation.

^aParameters estimated by simultaneous fitting of in vivo concentration-time data from intact and anhepatic patients, as detailed in the Materials and Methods.

^bInitial K_p values estimated using the Rodgers and Rowland (2006) method.

^cInitial CL_int data taken from microsomal substrate depletion assays in the presence of BSA. Full details are presented in Table 2.

^dCombined CL_int,P450 and CL_int,UGT data.