Influence of CYP2d6 on drug metabolism and methods for determining its activity
The article presents relevant information on the features of cytochrome P450 isoenzyme CYP2D6 functioning. 20-25% of drugs are metabolized by the action of CYP2D6. Determination of its activity allows for adjusting pharmacotherapy to increase the efficacy and safety of a drug or a combination of drugs. Cytochrome P450 isoenzymes genotyping and phenotyping methods allow for choosing the dosage and dosing regimen for patients on an individual basis. This article describes the genetic characteristics affecting CYP2D6. CYP2D6 polymorphism has a significant impact on pharmacokinetics and metabolism of a drug. This may lead to side effects, or decrease the pharmacological action of the drug. The article covers the cases of change in clinical response to receiving β-blockers (metoprolol), antidepressants (venlafaxine) and opioids (codeine). These changes occurred in the presence of certain CYP2D6 alleles which speed up or slow down the metabolism. It also provides information on drug-drug interactions involving inhibition of cytochrome P450 isoenzyme CYP2D6. Genotyping methods are used to determine the potential activity of CYP2D6. Dose adjustment is carried out basing on the results obtained. The current isoenzyme status is defined by phenotyping methods. CYP2D6 activity can be evaluated by determining the ratio of the substrate and its metabolite using HPLC. Pinoline, which is metabolized to 6-hydroxy-1,2,3,4-tetrahydro-β-carboline, is the endogenous substrate for estimating the activity of CYP2D6.