Drug metabolizing enzymes
Cytochrome P450 enzymes are the main drug metabolising enzymes (xenobiotic inactivators) in humans, and these are the primary contributors to Phase I oxidative metabolism of drugs and other chemicals.
The main families of CYP450 enzymes involved in drug metabolism are the monooxygenases of the CYP1, CYP2 and CYP3 families.
CYP3A4 is the most common and most versatile CYP450 enzyme involved in drug metabolism. Most drugs undergo deactivation by CYP3A4, whilst others are bioactivated to form their active compounds. CYP3A4 is inhibited by grapefruit, pomegranate and other fruit juices so patients should be made aware of the consequences of ingesting these juices whilst taking susceptible drugs.
Prescribers need to be aware of drug interactions with any of these enzymes that may alter responses to any other prescribed medications.
| Enzyme isoform | Drugs metabolised |
|---|---|
| CYP1A2 | |
| CYP2A6 |
coumarin |
| CYP2B6 | |
| CYP2C8 | |
| CYP2C9 |
cabozantinib (minor contribution) NSAIDs sulfonylureas |
| CYP2C19 |
tricyclic antidepressants tofacitinib (minor contribution) |
| CYP2D6 |
some antipsychotics some antiarrythmics some beta-blockers |
| CYP2E1 | |
|
|
HIV protease inhibitors calcium channel blockers (e.g. diltiazem, nifedipine and verapamil) many chemotherapeutics (e.g. docetaxel, paclitaxel and doxorubicin) many protein kinase inhibitors (e.g. sorafenib, imatinib, sunitinib and gefitinib) PDE5 inhibitors (sildenafil and tadalafil) |
The Liver and Drug Metabolism
This is a short interactive teaching resource provided by the University of Nottingham for their nursing and midwifery students. It guides the user easily through the drug metabolism process.
Clinically relevant CYP450 substrates, inhibitors and inducers.
This webpage produced by Indiana University Department of Medicine lists clinically relevant CYP450 enzyme substrate drugs, and drugs which either inhibit or induce CYP450 activities, tabulated against the corresponding enzyme subtype.
This web page provides a brief overview of the drug metabolism process, rate of metabolism, the cytochrome P450 enzymes of Phase I reactions and the effects of Phase II conjugation reactions. The information was written by Jennifer Le, PharmD, MAS, BCPS-ID.