Role of Pharmacist There is no guide, chart, or computer software program for clinicians to clearly identify or quickly predict which drugs interact with the CYP enzymes and create clinically significant drug interactions in patients. More research and clinical drug trials need to be conducted and reported on these enzymes and their interactions. With the knowledge of how cytochrome P450 enzymes enzymes work and of their physiologic role ... Read More

CYP2C Isoenzyme Metabolism The CYP2C subfamily consists of 2C9, 2C10, and 2C19 isozymes as well as others. While these enzymes metabolize a smaller number of drugs, many of these drugs are involved in clinically significant DIs. Drugs that are substrates for CYP2C isoenzymes include nonsteroidal anti-inflammatory drugs (NSAIDs) , phenytoin (2C9), S-warfarin (2C9), amiodarone (2C9), omeprazole and lansoprazole (2C19), and diazepam, clomipramine, amitriptyline and imipramine (2C). Common drugs that ... Read More

CYP1A2 Isoenzyme Metabolism Approximately 15% of all drugs used today are metabolized by the CYP1A2 isozyme. It is generally believed that there is no genetic polymorphism involved with this isozyme. Common drugs that are substrates for the CYP1A2 isozyme include R-warfarin, theophylline, caffeine, and some benzodiazepines, antidepressants and antipsychotics. Although few in number, these drugs are commonly involved with a large number of clinically significant DIs. The ... Read More

CYP2D6 Isoenzyme Metabolism About 25% of all drugs used today are substrates for the CYP2D6 isozyme. This isozyme has been studied extensively. It greatly exhibits genetic polymorphism; certain individuals will lack this enzyme from birth as a result of an autosomal recessive defect in its expression. Individuals lacking CYP2D6 will have a much larger pharmacologic response to usual doses of drugs metabolized by this enzyme and will have ... Read More

CYP3A4 Isoenzyme Metabolism The CYP3A enzyme family is composed of four isozymes involved with metabolism: CYP3A, CYP3A4, CYP3A5, and CYP3A7. Of these, the CYP3A4 isozyme is the most common; however, these enzymes are so closely related, they are often referred to collectively by their subfamily name, CYP3A. The CYP3A enzyme family is responsible for hepatic metabolism of approximately 60% of currently available pharmaceutical agents.A significant quantity of CYP3A4 isozyme is present ... Read More

Metabolism These CYP enzymes are present in every cell and are responsible for metabolizing or detoxifying consumed foreign (i.e., xeno) biological substances (e.g., toxins, carcinogens, mutagens and drugs). The enzymes primarily involved in drug metabolism are located in the liver. About 30 of these enzymes — especially the CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 isozymes — are primarily located in endoplasmic reticulum of hepatocytes in the liver and in the ... Read More

Genetic Polymorphism Genetic polymorphism plays a major role modulating drug interactions with the CYP metabolic enzyme system,and contributes to the classification of an individual as either a "poor metabolizer" or an "extensive metabolizer." Poor metabolizers probably lack a gene for certain isozymes and cannot metabolize certain drug substrates well while extensive metabolizers have the appropriate gene for the isozyme and metabolize drugs normally. Poor metabolizers may achieve toxic ... Read More

This installment focuses on drug interactions as a consequence of metabolism by the cytochrome P450 (CYP) enzyme system. Due to the complexity of this enzyme system and the massive amount of literature available on enzymatic interactions, this article will focus on some of the major drug interactions involving a limited number of the CYP enzymes. A patient case study and pharmaceutical care plan are included. The case ... Read More