P450 Enzyme | Substrate/Inhibitor | This Study | Perloff et al., 2009 a | Obach et al., 2007 a | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[HLM] | Time | Fold Dilution | IC50 | Fold Shift (B/C) | [HLM] | Time | Fold Dilution | IC50 | Fold Shift (B/C)a | [HLM] | Time | Fold Dilution | IC50 | Fold Shift (B/C)a | |||||
B | C | B | C | B | C | ||||||||||||||
mg · ml−1 | min | μM | mg · ml−1 | min | μM | mg · ml−1 | min | μM | |||||||||||
CYP1A2 | Phenacetin/furafylline | 0.1 | 5 | 10 | 3.4 | 0.036 | 94 | 0.2 | 10 | 10 | 8.4 | 0.021 | 400 | 0.03 | 30 | 10 | 1.5 | 0.027 | 56 |
CYP2B6 | Bupropion/ticlopidine | 0.1 | 5 | 10 | 0.20 | 0.039 | 5.1 | 0.1 | 5 | 10 | 0.84 | 0.048 | 18 | 0.05 | 20 | 10 | 0.13 | 0.031 | 4.2 |
CYP2C8 | Amodiaquine/gemfibrozil glucuronide | 0.0125 | 5 | 10 | 27 | 0.28 | 96 | 0.02 | 5 | 10 | 26 | 0.46 | 57 | 0.025 | 10 | 10 | N.D. | N.D. | N.D. |
CYP2C9 | Diclofenac/tienilic acid | 0.1 | 5 | 10 | 0.92 | 0.057 | 16 | 0.05 | 5 | 10 | 1.7 | 0.049 | 35 | 0.03 | 10 | 10 | 0.43 | 0.027 | 16 |
CYP2C19 | S-Mephenytoin/S-fluoxetine | 0.1 | 5 | 10 | 61 | 1.4 | 44 | 0.3 | 10 | 5 | 85 | 3.1 | 27 | 0.2 | 40 | 10 | N.D. | N.D. | N.D. |
CYP2D6 | Dextromethorphan/Paroxetine | 0.1 | 5 | 10 | 1.5 | 0.053 | 28 | 0.1 | 5 | 10 | 1.1 | 0.066 | 17 | 0.03 | 10 | 10 | 0.23 | 0.012 | 19 |
CYP3A4 | Midazolam/azamulin | 0.05 | 5 | 10 | 0.34 | 0.031 | 11 | 0.02 | 5 | 10 | 0.15 | 0.0025 | 60 | 0.03 | 4 | 10 | N.D. | N.D. | N.D. |
Midazolam/diltiazem | 0.05 | 5 | 10 | 78 | 1.2 | 65 | 0.02 | 5 | 10 | 100 | 3.4 | 29 | 0.03 | 4 | 10 | 54 | 3.7 | 15 | |
Midazolam/verapamil | 0.05 | 5 | 10 | 25 | 0.41 | 61 | 0.02 | 5 | 10 | 25 | 0.34 | 73 | 0.03 | 4 | 10 | 12 | 0.12 | 100 | |
CYP3A4 | Testosterone/azamulin | 0.1 | 5 | 10 | 0.46 | 0.044 | 10 | 0.05 | 10 | 10 | 0.098 | 0.0077 | 13 | 0.03 | 10 | 10 | N.D. | N.D. | N.D. |
Testosterone/diltiazem | 0.1 | 5 | 10 | 138 | 2.2 | 63 | 0.05 | 10 | 10 | 130 | 2.8 | 46 | 0.03 | 10 | 10 | 55 | 1.8 | 31 | |
Testosterone/verapamil | 0.1 | 5 | 10 | 29 | 0.38 | 76 | 0.05 | 10 | 10 | 28 | 0.27 | 104 | 0.03 | 10 | 10 | 8.2 | 0.15 | 55 |
N.D., no data.
↵a Calculated based on published values.