THE POTENTIAL ROLE OF CYP2D6 PHARMACOGENETICS ON CODEINE TOXICITY

Yıl 2017, Cilt: Volume 2 Sayı: İssue 1 (1) - 2.İnternational Congress Of Forensic Toxicology, 158 - 158, 16.02.2017

Zuhal Uçkun Sinan Süzen

Öz

Codeine, known
as 3-methylmorphine, is currently the most widely used opiate in the world.
Furthermore, codeine is one of the most commonly used drugs overall according
to WHO reports. Codeine is widely administered for the treatment of
postoperative pain, especially in paediatric patients. 

Pharmaceutical
drugs have been commonly implicated in drug-related deaths. It can be due to
the relationship between genetic polymorphisms and drug interactions on codeine
and morphine concentrations in codeine-related deaths.

Codeine is
mainly metabolized in the liver. Morphine, the product of codeine
O-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 0
to up to 75% of total codeine metabolism. Genetic polymorphisms are extremely
responsible for the inter-individual variation in enzyme expression and
activity. 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 Rapid
Metabolizers (UMs: CYP2D6XN); Extensive Metabolizers (EMs: CYP2D6 *2, *33,
*35); Intermediate Metabolizers (IMs: CYP2D6*9, *10, *17, *36 and *41); Poor
Metabolizers (PMs: CYP2D6 *3, *4, *5 and *6). The differences in drug
metabolism could lead to severe toxicity or therapeutic failure by altering the
relationship between the dose and the blood concentration of the
pharmacologically active parent drug or metabolite. As a result,
pharmacogenetic analysis may reveal new insight to the interpretation of
codeine toxicity.

Anahtar Kelimeler

THE POTENTIAL ROLE OF CYP2D6 PHARMACOGENETICS ON CODEINE TOXICITY

Kaynakça

• Zuhal UÇKUN, Sinan SÜZEN
• Department of Toxicology, Faculty of Pharmacy, University of Mersin, Mersin, Turkey Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey