Metabolic stability assay in human liver microsomes.
| Sample | HLM (final concentration of 0.5 mg protein per mL) | |||||
|---|---|---|---|---|---|---|
| R 2 a | t 1/2 b (min) | CLint(mic)c (μL min−1 mg−1) | CLint(liver)d (mL min−1 kg−1) | Remaining (T = 60 min) | Remaining (NCFe = 60 min) | |
| F-Id-3o | 0.9520 | 3.8 | 3.7 × 102 | 3.3 × 102 | 0.23% | 96% |
| PF74 | 1.0000 | 0.48 | 2.9 × 103 | 2.6 × 103 | 0.0% | 113% |
| Testosterone | 0.9982 | 17 | 83 | 74 | 7.9% | 91% |
| Diclofenac | 0.9947 | 3.7 | 3.7 × 102 | 3.3 × 102 | 0.0% | 97% |
| Propafenone | 0.9350 | 5.0 | 2.8 × 102 | 2.5 × 102 | 0.0% | 94% |
a
R 2 is the correlation coefficient of the linear regression to determine the kinetic constant (see raw data worksheet in the ESI†).
b
t 1/2 is half-life.
c
CLint(mic) = 0.693/t1/2/mg microsome protein per ml.
d
CLint(liver) = CLint(mic) × mg microsomal protein/g liver weight × g liver weight/kg body weight.
e
NCF: abbreviation of no co-factor. No NADPH is added to NCF samples (replaced by buffer) during the 60-minute incubation. If the NCF remaining is less than 60%, then possibly non-NADPH-dependent metabolism occurs.