TABLE 5

Sensitivity of digoxin clearance to flow, binding, transport, or intrinsic clearances: simulations with the PBPK model (control conditions: Q = 10 ml/min, with binding to red cells; k′rp = 1.81 min-1; kpr = 0.468 min-1 for the rbc-alb-perfused livers) (see Table 4)

Control Condition
Changes
Q = 40 ml/min
k′rp = kpr = 0
k′rp = kpr = 0 fp = 1
2 × CLin
 2 × CLef
 2 × CLint,met
 2 × CLint,sec
Hepatic clearance CLliver,tot (ml/min/g) 0.114 0.123 0.132 0.196 0.207 0.059 0.198 0.122
Metabolic clearance CLliver,met (ml/min/g) 0.105 0.113 0.122 0.180 0.190 0.055 0.190 0.104
Biliary clearance CLliver,ex (ml/min/g) 0.009 0.010 0.011 0.016 0.017 0.005 0.008 0.018
CLliver,met/CLliver,ex
11.4
11.4
11.4
11.4
11.4
11.4
22.7
5.7