Estimated input parameters for static model prediction of M/P drug ratios
The constants are Qh = 21 ml/min/kg, Qgut = 4 ml/min/kg; 45 mg microsomes/gm liver,20 gm liver/kg/b.wt., and 2978 mg microsomes/whole intestine (i.e., 42 mg intestinal microsomes/kg/b.wt.).
| Parameter | Input Values | Scaled Value |
|---|---|---|
| TBPT | ||
| CLp | fu = 0.38; B/P = 0.86; CLint = 32 µl/min/mg | 7.9 ml/min/kg |
| Fh | CLp = 7.9 ml/min/kg | 0.62 |
| Fg | fu = 0.38; B/P = 0.86; CLint = 13 µl/min/mg | 0.94 |
| Metabolite M1 | ||
| CLm | fu = 0.64; B/P = 0.88; CLint = 32 µl/min/mg | 11 ml/min/kg |
| fCL,m | CLint,TBPT = 32 µl/min/mg; CLint,TBPT→M1 = 12 µl/min/mg | 0.38 or 0.41a |
| Fm | fu = 0.64; B/P = 0.88; CLint = 32 µl/min/mg | 0.47 |
| fgutCL,m | CLint,TBPT = 13 µl/min/mg; CLint,TBPT → M1 = 3.4 µl/min/mg | 0.26 or 0.30a |
| Fm,gut | Assumed as unity | 1 |
| Metabolite M2 | ||
| CLm | fu = 0.0025; B/P = 0.53; CLint = 102 µl/min/mg | 0.40 ml/min/kg |
| fCL,m | CLint,TBPT = 32 µl/min/mg; CLint,TBPT → M2 = 2.5 µl/min/mg | 0.08 or 0.41a |
| Fm | fu = 0.0025; B/P = 0.53; CLint = 102 µl/min/mg | 0.98 |
| fgutCL,m | CLint,TBPT = 13 µl/min/mg; CLint,TBPT → M2 = 1.4 µl/min/mg | 0.11 or 0.58a |
| Fm,gut | Assumed as unity | 1 |
B/P, blood-to-plasma ratio.
↵a Values are corrected for by secondary metabolism (see Materials and Methods).