TABLE 5

Statistical analysis of clearance predictions for 72 drugs using recombinant cytochrome P450 enzymes

Scaling methods 1 and 2 compare the relative activity and abundance methods for clearance predictions. Methods 1 and 3 assess the importance of blood distribution parameters, specifically the free fraction in blood for in vivo intrinsic clearance calculation. Methods 1 and 4 assess the importance of in vitro binding and methods 1 and 5 compare the PT and WS models for in vivo intrinsic clearance estimation.

Method 1
Method 2
Method 3
Method 4
Method 5
Scaling parameters
    Scaling method Activity Abundance Activity Activity Activity
    Blood distribution ✓ ✓ ✓ ✓ ✓
    Liver model PT PT PT PT WS
    Nonspecific binding ✓ ✓ ✓ Embedded Image ✓
Statistics
    r2 0.42 0.44 0.05 0.35 0.37
    afe 1.53 2.08 5.41 2.08 2.15
    rmse 1528 2352 1820 2548 17920
    % Inside 2-fold error 32 34 12 26 27
    % Inside 5-fold error
73
71
45
68
66