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 oxygen atom is inserted into the substrate (the drug), and the other is reduced to water. Thus, the original substrate is rendered more polar and water-soluble. If the metabolites are polar enough, they can be excreted. However, most products undergo another reaction, which will be discussed later.
CYP enzymes deactivate most drugs, 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 | Barbiturates, citalopram, mephenytoin, phenytoin, R-warfarin, THC |
| CYP2D6 | Tricyclic antidepressants, antipsychotics (e.g., haloperidol), anti-arrhythmias (e.g., flecainide), beta-blockers (e.g., 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 (e.g., terfenadine, astemizole), calcium channel blockers (e.g., felodipine), cannabinoids, cyclosporine, macrolides (e.g., erythromycin), buprenorphine, protease inhibitors (e.g., ritonavir), tacrolimus, midazolam, nefazodone, oxycodone |
