Examples of recommended in vitro probe substrates and inhibitors for P450s (adapted from Tucker et al., 2001)
P450 | Substrates | Inhibitorsa | ||||
|---|---|---|---|---|---|---|
|
Preferred
|
Acceptable
|
Preferred
|
Acceptable
| |||
| CYP1A2 | Ethoxyresorufin, phenacetin | Caffeine (low turnover), theophylline (low turnover), acetanilide (mostly applied in hepatocytes), methoxyresorufin | Furafylline | α-Naphthoflavone (but can also activate and inhibit CYP3A4) | ||
| CYP2A6 | Coumarin | 8-Methoxypsoralen | Coumarin (but high turnover), Sertraline (but also inhibits CYP2D6) | |||
| CYP2B6 | S-Mephenytoin (N-desmethyl metabolite) | Bupropion (availability of metabolite standards?) | ||||
| CYP2C8 | Paclitaxel (availability of standards?) | Glitazones (availability of standards?) | ||||
| CYP2C9 | S-Warfarin, diclofenac | Tolbutamide (low turnover) | Sulphaphenazole | |||
| CYP2C19 | S-Mephenytoin (4-hydroxy metabolite), omeprazole | Ticlopidine (but also inhibits CYP2D6), nootkatone (but also inhibits CYP2A6) | ||||
| CYP2D6 | Bufuralol dextromethorphan | Metoprolol, debrisoquine, codeine (all with no problems, but less commonly used) | Quinidine | |||
| CYP2E1 | Chlorzoxazone | 4-Nitrophenol, lauric acid | Clomethiazole | 4-Methyl pyrazole | ||
|
CYP3A
|
Midazolam, testosterone (strongly recommended that at least two structurally
unrelated substrates be used)
|
Nifedipine, felodipine, cyclosporin A, terfenadine, erythromycin, simvastatin
|
Ketoconazole (but recent evidence indicates that it is also a potent inhibitor
of CYP2C8), troleandomycin
|
Cyclosporin A
| ||
↵ a Specific inhibitory antibodies may also be used.