TY - JOUR TT - THE POTENTIAL ROLE OF CYP2D6 PHARMACOGENETICS ON CODEINE TOXICITY AU - Uçkun, Zuhal AU - Süzen, Sinan PY - 2017 DA - February JF - The Turkish Journal Of Occupational / Environmental Medicine and Safety JO - turjoem PB - Engin TUTKUN WT - DergiPark SN - 2149-4711 SP - 158 EP - 158 VL - Volume 2 IS - İssue 1 (1) KW - THE POTENTIAL ROLE OF CYP2D6 PHARMACOGENETICS ON CODEINE TOXICITY N2 - Codeine, knownas 3-methylmorphine, is currently the most widely used opiate in the world.Furthermore, codeine is one of the most commonly used drugs overall accordingto WHO reports. Codeine is widely administered for the treatment ofpostoperative pain, especially in paediatric patients.  Pharmaceuticaldrugs have been commonly implicated in drug-related deaths. It can be due tothe relationship between genetic polymorphisms and drug interactions on codeineand morphine concentrations in codeine-related deaths.Codeine ismainly metabolized in the liver. Morphine, the product of codeineO-demethylation by the highly polymorphic enzyme cytochrome P450 2D6 (CYP2D6),is the metabolite primarily responsible for the analgesic effect of codeine.The amount of morphine formed from codeine is highly variable, ranging from 0to up to 75% of total codeine metabolism. Genetic polymorphisms are extremelyresponsible for the inter-individual variation in enzyme expression andactivity. In contrast to other CYPs, CYP2D6 is not inducible, consequently,there is a large inter-individual variation in the enzyme activity of CYP2D6.Phenotyping for CYP2D6 have four types of metabolizers – Ultra RapidMetabolizers (UMs: CYP2D6XN); Extensive Metabolizers (EMs: CYP2D6 *2, *33,*35); Intermediate Metabolizers (IMs: CYP2D6*9, *10, *17, *36 and *41); PoorMetabolizers (PMs: CYP2D6 *3, *4, *5 and *6). The differences in drugmetabolism could lead to severe toxicity or therapeutic failure by altering therelationship between the dose and the blood concentration of thepharmacologically active parent drug or metabolite. As a result,pharmacogenetic analysis may reveal new insight to the interpretation ofcodeine toxicity. CR - Zuhal UÇKUN, Sinan SÜZEN CR - Department of Toxicology, Faculty of Pharmacy, University of Mersin, Mersin, Turkey Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey UR - https://dergipark.org.tr/tr/pub/turjoem/issue//306118 L1 - https://dergipark.org.tr/tr/download/article-file/293870 ER -