W-3 Enzymes

CYP1A2 Enzyme by Kourtnee Fitzgerald

Cytochrome P450 is a family of enzymes that influence drug metabolism (Stahl, 2013; Woo & Robinson, 2020). Patients may have genetic mutations or polymorphisms of these enzymes which can impact their ability to metabolize certain drugs, and the extent of adverse reactions they may experience (McDonnell & Dang, 2013). CYP1A2 is part of this family of enzymes and comprises around 13% of CYP in the liver (Thorn et al., 2012). It contains several haplotypes including CYP1A2 *1A, 1F, 1C, and 1K (Thorn et al., 2012). This enzyme has a large role in activation of toxic xenobiotics, so has been studied not only for its role in drug metabolism, but also for its role in cancer risk and metabolism of carcinogens (Thorn et al., 2012). Smoking is an inducer of this enzyme, which can cause patients to require increased doses of medications that are substrates of CYP1A2 (Stahl, 2013). Medications that are substrates of this enzyme include olanzapine, duloxetine, and even ondansetron (McDonnell & Dang, 2013). CYP1A2 is essential to clozapine metabolism, and patients who are ultra-rapid metabolizers receive improved outcomes with increased dosing or co-administration of a CYP1A2 inhibitor such as fluvoxamine (Thorn et al., 2012).

References:

McDonnell, A. M., & Dang, C. H. (2013). Basic review of the cytochrome p450 system. Journal of the Advanced Practitioner in Oncology, 4(4), 263–268. https://doi.org/10.6004/jadpro.2013.4.4.7

Stahl, S. (2013). Essentials of psychopharmacology, (4th edition). United Kingdom, Cambridge University

Thorn, C. F., Aklillu, E., Klein, T. E., & Altman, R. B. (2012). PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenetics and Genomics, 22(1), 73–77. https://doi.org/10.1097/FPC.0b013e32834c6efd

Woo, T. M., & Robinson, M. V. (2020). Pharmacotherapeutics for advanced practice nurse prescribers (5th ed.). Philadelphia, PA: F.A. Davis Company.