Table 3.
Metabolic stability assay in human liver microsomes.
| Sample | HLM (Final concentration of 0.5 mg protein/mL) |
|||||
|---|---|---|---|---|---|---|
| R2a | T1/2b (min) | CLint(mic)c (µL/min/mg) | CLint(liver)d (mL/min/kg) | Remaining (T = 60min) | Remaining (NCFe = 60min) | |
| 7m | 0.9055 | 25.7 | 53.9 | 48.5 | 17.0% | 100.1% |
| 7u | 0.9028 | 54.6 | 25.4 | 22.8 | 42.2% | 92.4% |
| PF74 | 1.0000 | 0.5 | 2862.5 | 2576.2 | 0.0% | 112.6% |
| Testosterone | 0.9982 | 16.7 | 82.8 | 74.5 | 7.9% | 90.7% |
| Diclofenac | 0.9947 | 3.7 | 372.0 | 334.8 | 0.0% | 96.7% |
| Propafenone | 0.9350 | 5.0 | 279.5 | 251.5 | 0.0% | 93.6% |
a
R2 is the correlation coefficient of the linear regression for the determination of the kinetic constant.
b
T1/2 is the 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 a non-NADPH dependent reaction occurs.