Table 3.
Metabolic stability assay in human liver microsomes
| HLM (Final concentration of 0.5 mg protein/mL) | ||||||
|---|---|---|---|---|---|---|
| Sample | R2 a | T1/2b (min) |
CLint(mic)c (μL/min/mg) |
CLint(liver)d (mL/min/kg) |
Remaining (T=60min) |
Remaining (NCFe=60min) |
| 6a-9 | 1.0000 | 0.9 | 1559.4 | 1403.5 | 0.3% | 122.1% |
| PF-74 | 1.0000 | 0.6 | 2403.0 | 2162.7 | 0.0% | 95.4% |
| Testosterone | 0.9239 | 7.4 | 188.3 | 169.4 | 3.6% | 74.4% |
| Diclofenac | 0.9924 | 5.6 | 248.2 | 223.4 | 0.5% | 95.9% |
| Propafenone | 0.9616 | 5.4 | 257.7 | 231.9 | 0.1% | 97.9% |
a
R2 is the correlation coefficient of the linear regression for determination of the kinetic constant.
b
T1/2 is half-life and CLint(mic) is the intrinsic clearance.
c
CLint(mic) = (0.693/half-life)/mg microsome protein per mL.
d
CLint(liver) = CLint(mic) × mg microsomal protein/g liver weight × g liver weight/kg body weight.
e
NCF: no cofactor. No NADPH regenerating system was added to the NCF sample (replaced by buffer) during the 60 min incubation. If the remaining amount is less than 60%, then non-NADPH dependent reaction occurs.