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

	Propranolol	Imipramine	Warfarin
f_u(serum)	0.12	0.06	0.008
f_u(blood) ^3-a	0.13	0.05	0.014
f_{u(microsomes)}	0.38	0.16	0.73
Serum-microsome partitioning (f_u(serum)/f_{u(microsomes)})_{(partitioning)}	0.26	0.31	0.033
Total in vitro Cl′_int(ml/min/kg)	48	48	1.2
Predicted human blood clearance (ml/min/kg) from equations:
Well-stirred model
Eq. 1: All protein binding ignored	15	15	1.1
Eq. 2: Including only f_u(blood)	4.8	2.2	0.017
Eq. 3: Including f_u(blood) and f_{u(microsomes)}	9.2	8.6	0.023
Eq. 4: Including serum-microsome partitioning	8.4	9.0	0.072
Parallel tube model
Eq. 5: All protein binding ignored	19	19	1.1
Eq. 6: Including only f_u(blood)	5.3	2.4	0.016
Eq. 7: Including f_u(blood) and f_{u(microsomes)}	11	11	0.023
Eq. 8: Including serum-microsome partitioning	10	11	0.072
Human plasma clearance (ml/min/kg)	14^3-c	15^3-b	0.045^3-b
Human blood clearance (ml/min/kg)	16^3-b	14^3-c	0.081^3-c

Equations referred to in the table are as follows:^e
Well-stirred model: $\text{[math]}$ Equation 1 $\text{[math]}$ Equation 2 $\text{[math]}$ Equation 3 $\text{[math]}$
Parallel-tube model: $\text{[math]}$ Equation 5 $\text{[math]}$ Equation 6 $\text{[math]}$ Equation 7 $\text{[math]}$
↵3-a f_u(blood) = f_u(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).