Summary of estimated unbound metabolic clearance (CLint,u) values
A, the standard method with fuinc being predicted from lipophilicity, described by eq. 1 (CLint,u = CLint/fuinc); B, the fit to CLint data from several hepatocyte concentrations (eq. 2, estimated S.E. in parenthesis).
| Drug | Log D7.4 | A | B | ||
|---|---|---|---|---|---|
| CLint,u | fuinc | CLint,u | fuinc | ||
| μl/min per 1 million cells | 1 million cells/ml | μl/min per 1 million cells | 1 million cells/ml | ||
| AZ151 | 2.41 | 40 | 0.72 | 38 (2.0) | 0.78 (0.045) |
| Atorvastatin | 1.1 | 25 | 0.90 | 68 (6.1) | 0.33 (0.049) |
CLint,u, unbound intrinsic clearance from hepatocyte incubation; fuinc, fraction unbound in the incubation.