TABLE 5

Simulations of hepatic metabolic, biliary, and total clearances with changes in the secretion and metabolism intrinsic clearances and the efflux and influx clearances a

The values are given by the product of the shown percentage and the corresponding CLinflux, CLefflux, CLint,met, and CLint,sec; the bold arrows denote the change in the hepatic metabolic, biliary, or total clearances.



Parameters

Predicted Changes

Increased Secretion Example 1
Increased Metabolism Example 2
Decreased Secretion Example 3
Decreased Metabolism Example 4
Decreased Secretion; Decreased Efflux Example 5
Decreased Secretion; Decreased Efflux Example 6
CLinflux (ml/min/g) 4.00 Same Same Same Same Same Same
CLefflux (ml/min/g) 1.46 Same Same Same Same 50% 90%
CLint,met (ml/min/g) 0.61 Same 200% Same 50% Same Same
CLint,sec (ml/min/g) 0.0388 500% Same 50% Same 50% 10%
Hepatic metabolic clearance CLliver,met (ml/min/g) 0.345 0.300 (↓) 0.434 (↑) 0.351 (↑) 0.244 (↓) 0.434 (↑) 0.523 (↑)
Biliary clearance CLliver,ex (ml/min/g) 0.022 0.095 (↑) 0.014 (↓) 0.011 (↓) 0.031 (↑) 0.014 (↓) 0.030 (↑)
Total hepatic clearance CLliver,tot (ml/min/g) 0.367 0.395 (↑) 0.448 (↑) 0.362 (↓) 0.275 (↓) 0.448 (↑) 0.553 (↑)
CLliver,met/CLliver,ex = CLint,met/CLint,sec 15.7 3.1 31.4 31.4 7.9 31.4 17.4
Calculated CT,ss/CP,ssa
1.9
1.77
1.47
1.91
2.22
2.94
5.06
  • a fPCLinflux/[fL(CLefflux + CLint,met + CLint,sec)].