Table 4 CYP inhibition and induction activity for compounds 4 and 5
CYP inhibition | |||||
|---|---|---|---|---|---|
CYP Isozyme | CYP Substrate | IC50 (μM) | |||
Cmpd 4 | Cmpd 5 | Rifabutin | Rifampicin | ||
1A2 | Phenacetin | 10.9 | 2.02 | ND | ND |
2B6 | Bupropion | 11.6 | 2.98 | ND | ND |
2C8 | Amodiaquine | 6.76 | 1.99 | ND | ND |
2C9 | Diclofenac | ND | 4.65 | ND | ND |
2C19 | Mephenytoin | 9.99 | 2.54 | ND | ND |
2D6 | Dextromethorphan | 11.7 | 2.81 | ND | ND |
3A4 | Midazolam | 8.05 | 2.71 | 17.5 | ND |
3A4 | Testosterone | 5.66 | 2.15 | 36 | ND |
CYP induction | ||||
|---|---|---|---|---|
Compound Number | Fold Induction (Enzyme Activity) | Average % Stability | ||
CYP 1A2 | CYP 2B6 | CYP 3A4 | ||
4 | 0 | 0.0131 | 0.128 | 75.8 |
5 | 0 | 0.0131 | 0.128 | 53.7 |
Rifabutin | 2 | 2.65 | 2.36 | 77.8 |
Rifampicin | 1.33 | 10.8 | 11.8 | 85.2 |
