The CYP enzymes involved in drug metabolism are:
- CYP3A4 (responsible for approximately 40-50% of all drug metabolism)
- CYP2D6 (responsible for approximately 20-30% of all drug metabolism)
- CYP1A2
- CYP2C9
- CYP2C19
- CYP2E1
- CYP2B6
- CYP2A6
The following equation illustrates how CYP enzymes facilitate the addition of oxygen to a lipophilic drug to make it more polar and, thus, water soluble:
One atom of oxygen is inserted into the substrate (the drug). The other oxygen atom is reduced to water. The original substrate is now rendered more polar and thus water soluble. If the metabolites are polar enough, they can be excreted. However, most products undergo another, additional reaction which will be discussed later.
Most drugs are deactivated by CYP enzymes, but some are bio-activated to form active metabolites. An example is the conversion of codeine to morphine.
| Substrates of Cytochrome P450 Enzymes |
| CYP1A1 | Polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides |
| CYP1A2 | Amitriptyline, imipramine, clozapine, haloperidol, propranolol, theophylline, verapamil, R-warfarin |
| CYP1B1 | Tamoxifen, aflatoxins |
| CYP2A6 | Coumarins, aflatoxins, valproate |
| CYP2B6 | Bupropion, coumarins, methadone, ketamine |
| CYP2C8 | Amodiaquine, cerivastatin, tolbutamide |
| CYP2C9 | Amitriptyline, fluoxetine, NSAIDs, phenytoin, tamoxifen, S-warfarin, THC |
| CYP1C19 | Barbituates, citalopram, mephenytoin, phenytoin, R-warfarin, THC |
| CYP2D6 | Tricyclic antidepressants, antipsychotics (eg, haloperidol) anti-arrythmics (eg, flecainide)), beta-blockers (eg, timolol), MDMA, selective serotonin reuptake inhibitors (SSRIs), tramadol, codeine, venlafaxine, methamphetamine, amphetamine, codeine, hydrocodone, oxycodone |
| CYP2E1 | Ethanol, flurane anesthetics (eg, halothane, paracetamol) |
| CYP3A4/5 | Antihistamines (eg, terfenadine, astemizole), calcium channel blockers (eg, felodipine), cannabinoids, cyclosporine, macrolides (eg, erythromycin), buprenorphine, protease inhibitors (eg, ritonavir), tacrolimus, midazolam, nefazodone, oxycodone |
