Metabolic capacity of CYP2D6 within an Iranian population (Mazandaran Province)

Background: CYP2D6 is polymorphically expressed enzyme that show marked interindividual and interethnic variation. Phenotyping of CYP2D6 provides valuable information about real-time activity of this important drug-metabolizing enzymes through the use of specific probe drugs. The aim of this study was to identify the CYP2D6 oxidation phenotype with dextromethorphan (DEX) as a probe drug in Mazandarani ethnic group among Iranian population. Methods: The study included 71 unrelated healthy volunteers. Dextromethorphan hydrobromide (30 mg) was given orally to healthy subjects and peripheral venous blood samples (10 ml) were taken at 3 hr post-dose. Dextromethorphan and the metabolite dextrorphan (DOR) were analyzed by the HPLC method. The log DEX/DOR metabolic ratio (MR) at 3 hr plasma sample was used as the index of CYP2D6 activity and a value of 0.3 was used as the antimode separating extensive metabolizers (EM) and poor metabolizers (PM) phenotypes. Results: A 560-fold interindividual variation in dextromethorphan MRs was observed in this study. Considering the antimode 0.3 in log scale, 7.04% (5/71) volunteers were identified as PMs.Conclusion: The result showed that the frequency of CYP2D6 PM phenotypes accounted for 7.04% of subjects in our samples. Despite these findings, we propose a further study in larger samples to provide a wider image and to get more valuable information upon pharmacogenetic basis for individual therapy and personalized medicine.