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: Equation 1 Equation 2 Equation 3
Parallel-tube model: Equation 5 Equation 6 Equation 7
↵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).