The cytochrome P450 (CYP) enzymes are a protein superfamily involved in the synthesis and metabolism of drugs, toxins and normal cellular components.
“Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. Genetic variability (polymorphism) in these enzymes may influence a patient's response to commonly prescribed drug classes, including beta blockers and antidepressants. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes.” (Lynch, 2007)
The population variability of CYP3A4 activity is extremely high, so a genetic testing may be required.
CYP2D6, 2C19, and 2C9 polymorphisms account for the most frequent variations in phase I metabolism of drugs, since almost 80% of drugs in use today are metabolized by these enzymes. Approximately 5-14% of Caucasians, 0-5% Africans, and 0-1% of Asians lack CYP2D6 activity, and these individuals are known as poor metabolizers.
IMPLICATIONS-example: According to the FDA-approved drug label for carbamazepine, testing for HLA-B*15:02 should be done for all patients with ancestry in populations with increased frequency of HLA-B*15:02, prior to initiating carbamazepine therapy
Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007 Aug 1;76(3):391-6. PMID: 17708140.
Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev. 2009;41(2):89-295. doi: 10.1080/03602530902843483. PMID: 19514967.