It is located on chromosome 22 and consists of 4382 nucleotides. CYP2D6 codes for an enzyme that is composed of 497 amino acids. The CYP2D6 enzyme plays a primary role in the metabolism of more than 70 substrate medications, including twelve psychotropic medications. CYP2D6 is one of the most highly variable drug-metabolizing enzyme genes. However,

Inhibitors,research,lifescience,medical many of the other 29 P450 drug-metabolizing enzyme genes are also highly variable. The specific genetic variations that define variable phenotypes can be located on a Web site maintained by the Karolinska Institute (http://www.HTS assay cypalleles.ki.se/). Each newly identified variant is included on the Web site after confirmation that it is unique. There are currently 75 distinct CYP2D6 alleles posted

on this site, as well as an additional 55 CYP2D6 variants that closely resemble one of the primary Inhibitors,research,lifescience,medical variants. Traditionally, these variants have been classified as being normal, deficient, or inactive drug-metabolizing alleles. Additionally, some alleles have more recently been demonstrated to code for Inhibitors,research,lifescience,medical an increased amount of enzyme which enhances the metabolic activity of the patient. Furthermore, patients can have a variable number of copies of CYP2D6. The most common number of copies of CYP2D6 that patients carry is two. However, some patients have only one copy and, rarely, none at all. It is also possible to have more than two copies, and one patient has been reported to have 13 copies.4 The development of several different classification systems to categorize 2D6 substrate metabolic capacity of patients into four phenotypic categories has been Inhibitors,research,lifescience,medical problematic. The use of alternative methodologies by different research teams has made it more difficult to study the implications of this Inhibitors,research,lifescience,medical variability. The most

important CYP2D6 phenotype to identify is the poor 2D6 substrate metabolizer phenotype. Patients who are poor metabolizers are at increased risk for adverse events when they are prescribed 2D6 substrate medications, because of of their low metabolic capacity. Patients are now classified as poor metabolizers if they have two inactive alleles, or one inactive allele and one deficient allele. The second most clinically important CYP2D6 phenotype is the ultrarapid metabolizer phenotype. Patients are ultrarapid metabolizers if they have either three or more active copies of CYP2D6 or two or more enhanced copies of CYP2D6. They are unlikely to respond to 2D6 substrate medications at standard doses because their ability to rapidly metabolize these medications makes it difficult to sustain therapeutic serum levels. The third clinically important CYP2D6 phenotype is the intermediate metabolizer phenotype. These patients have one normal copy of CYP2D6, and one copy that is either deficient or inactive.