Table 3

Human blood clearance values obtained by scaling of in vitrointrinsic clearance data using equations describing the well-stirred and parallel tube models of hepatic clearance and including or excluding serum protein and microsome binding

fu(blood) 3-a
fu(microsomes) 0.380.160.73
Serum-microsome partitioning (fu(serum)/fu(microsomes))(partitioning) 0.260.310.033
Total in vitro Cl′int(ml/min/kg)48481.2
Predicted human blood clearance (ml/min/kg) from equations:
Well-stirred model
 Eq. 1: All protein binding ignored15151.1
 Eq. 2: Including only fu(blood)
 Eq. 3: Including fu(blood) and fu(microsomes)
 Eq. 4: Including serum-microsome partitioning8.49.00.072
Parallel tube model
 Eq. 5: All protein binding ignored19191.1
 Eq. 6: Including only fu(blood)
 Eq. 7: Including fu(blood) and fu(microsomes) 11110.023
 Eq. 8: Including serum-microsome partitioning10110.072
Human plasma clearance (ml/min/kg)143-c 153-b 0.0453-b
Human blood clearance (ml/min/kg)163-b 143-c 0.0813-c
  • Equations referred to in the table are as follows:e

  • Well-stirred model:Formula Equation 1Formula Equation 2Embedded Image Equation 3Embedded Image

  • Parallel-tube model:Embedded Image Equation 5Embedded Image Equation 6Embedded Image Equation 7Embedded Image

  • 3-a fu(blood) = fu(serum)/blood to plasma ratio.

  • 3-b Values from Goodman and Gilman’s “Pharmacological Basis of Therapeutics” 9th edition (1996). Note that the values for propranolol differ from those listed in ref. 9(plasma clearance = 9.3 ml/min/kg; blood clearance = 12 ml/min/kg) and the values for imipramine differ from those in ref. 13(plasma clearance = 14 ml/min/kg).

  • 3-c Blood clearance = plasma clearance/blood to plasma ratio; 0.89 for propranolol (Goodman and Gilman), 1-hematocrit (0.55) for warfarin (ref. 10), 1.1 for imipramine (Goodman and Gilman).

  • 3-d B/P = blood to plasma ratio.

  • 3-e A value of 21 ml/min/kg was used for Q (human hepatic blood flow).