INTERPLAY OF DRUG TRANSPORTERS AND ENZYMES ON HEPATIC DRUG PROCESSING - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 732

Oatp1a1

Oatp1a4

Oatp1b2

Mrp2

Sult1a1

Sult1e1

Sult2a1

Sham-operated Peritumor

(a)

2

Sham-operated tissue
Peritumor tissue

*

1

*

*

0

Oatp1a1 Oatp1a4 Oatp1b2 Mrp2 Sult1a1 Sult1e1 Sult2a1

(b)

FIGURE 23.14. Western blots (relative protein expression) ( a ) and integrated densitometric
analysis ( b ) of crude membrane fractions (for the Oatps and Mrp2) and cytosolic fractions (for
Sult's) prepared from sham-operated rat liver tissue ( n = 4) and peritumor tissue of metastatic
rat livers ( n = 5). An asterisk denotes that p < 0 . 05 between sham-operated and peritumor
tissue. (From ref. 105, with permission.)

Due to futile cycling, equation (7) no longer holds even for the PBPK model; the
ratio CL liver , met /CL liver , sec fails to reflect CL int , sult /CL int , sec (2.56/1.55 or 1.65) (Table
23.8). Due to the high extraction ratio for E 2 17G, clearance values would change more
dramatically between the PBPK and ZPBPK models that engender heterogeneity
even when the same given intrinsic clearance is used for prediction (Table 23.8).
The ZPBPK model consists of variable CL int , sult , i for sulfation in the PP, midzonal,