TABLE 9

Pharmacokinetics of FK506 and digoxin in perfused rat liver preparation with and without inhibitors


Inhibitors

Biliary Clearance (ml/min)

Metabolism or Metabolic Clearance (ml/min)

AUC

CLliver,tot (ml/min)

Reference
FK506 (100 μg)
+ Troleandomycin (Cyp3a inhibitor) Not measured Not measured Increaseda Decreaseda Wu and Benet (2003)
+ GG918 (P-glycoprotein inhibitor) Not measured Not measured Decreasedb Increasedb
+ Cyclosporine (Cyp3a and P-glycoprotein inhibitor) Not measured Not measured Increaseda Decreaseda
Digoxin (10 μg)
+ Rifampicin 100 μM (Oatp2 inhibitor) Not measured Decreaseda Increaseda Decreaseda Lau et al. (2004)
+ Quinidine 10 μM (P-glycoprotein inhibitor)
Not measured
Increaseda
Decreasedb
Increasedb

  • a Expected outcome.

  • b Unexpected outcome; CLliver,tot should not increase upon inhibited secretion; occurs only if efflux is inhibited (similar to example 5, Table 5).