CYP2C8

Ligands

Following is a table of selected substrates, inducers and inhibitors of 2C8.

Inhibitors of CYP2C8 can be classified by their potency, such as:

• Strong inhibitor being one that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
• Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
• Weak inhibitor being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance.

Where classes of agents are listed, there may be exceptions within the class.

Epoxygenase activity

CYP2C8 also possesses epoxygenase activity: it is one of the principal enzymes responsible for attacking various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. It metabolizes: 1) arachidonic acid to various epoxyeicosatrienoic acids (also termed EETs); 2) linoleic acid to 9,10-epoxy octadecenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).

Along with CYP2C8, CYP2C9, CYP2C19, CYP2J2, and possibly CYP2S1 are the main producers of EETs and, very likely, EEQs, EDPs, and the epoxides of linoleic acid.

References

References

1. (Nov 2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators.
2. Flockhart DA. (2007). "Drug Interactions: Cytochrome P₄₅₀ Drug Interaction Table". [[Indiana University School of Medicine]].
3. (2007). "Rang & Dale's pharmacology". Churchill Livingstone.
4. Product Information: PLAVIX(R) oral tablets, clopidogrel bisulfate oral tablets. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership (per FDA), Bridgewater, NJ, 2019. https://packageinserts.bms.com/pi/pi_plavix.pdf {{Webarchive. link. (2021-06-12)
5. (October 2014). "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease". Pharmacological Reviews.
6. (October 2014). "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators.
7. (March 2014). "Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway". Journal of Lipid Research.
8. (April 2015). "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.
9. (November 2014). "Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders". Pharmacology & Therapeutics.