TABLE 1

Impact of increasing fraction unbound in plasma

Administration route and drug characteristics.

Parameter	Par Low E Low V	Par Low E High V	Par High E Low V	Par High E High V	Oral Low E Low V	Oral Low E High V	Oral High E Low V	Oral High E High V
CL total	↑	↑	—	—	↑	↑	—	—
C_max total	↓	↓	—	↓	↓	↓	↓	↓
C_ss total	↓	↓	—	—	↓	↓	↓	↓
C_max unbound	↑	—	↑	↑	↑	—	—	↓
C_ss unbound	—	—	↑	↑	—	—	—	—

CL, total drug clearance; high E, high extraction ratio; high V, high volume of distribution (distributes extensively to peripheral tissues); low E, low extraction ratio; low V, low volume of distribution (confined primarily to central compartment); oral, oral administration; par, parenteral administration.