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 | |
|---|---|---|---|
| fu(serum) | 0.12 | 0.06 | 0.008 |
| fu(blood) 3-a | 0.13 | 0.05 | 0.014 |
| fu(microsomes) | 0.38 | 0.16 | 0.73 |
| Serum-microsome partitioning (fu(serum)/fu(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 fu(blood) | 4.8 | 2.2 | 0.017 |
| Eq. 3: Including fu(blood) and fu(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 fu(blood) | 5.3 | 2.4 | 0.016 |
| Eq. 7: Including fu(blood) and fu(microsomes) | 11 | 11 | 0.023 |
| Eq. 8: Including serum-microsome partitioning | 10 | 11 | 0.072 |
| 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 |
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Equations referred to in the table are as follows:e
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Well-stirred model:
Equation 1
Equation 2
Equation 3
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Parallel-tube model:
Equation 5
Equation 6
Equation 7
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↵3-a fu(blood) = fu(serum)/blood to plasma ratio.
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↵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).
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↵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).
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3-d B/P = blood to plasma ratio.
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3-e A value of 21 ml/min/kg was used for Q (human hepatic blood flow).
