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Published on: March 28, 2017
CYP2D6 phenotyping with dextromethorphan
Anna Wojtczak1, Mariola Rychlik-Sych, Eliza Krochmalska-Ulacha
1Department of Pharmacogenetics, Medical University of Łódź, Muszyńskiego 1, PL 90-151 Łódź, Poland. awojt@mp.pl
Abstract:
Genetically determined individual differences in the ability to oxidize certain drugs have raised recently a considerable interest because of clinical importance of this problem. Determination of CYP2D6 oxidation phenotype is used to obtain more efficient pharmacotherapy and to explain lower efficacy of some drugs and presentation of adverse effects in particular patients. The aim of this study was to identify the CYP2D6 oxidation phenotype with dextromethorphan (DM) as a probe drug. The study included 85 healthy volunteers of Polish origin. DM (40 mg) was given orally to healthy adults and 10-h urine samples were collected. DM and the metabolite dextrorphan (DX) were analyzed by the HPLC method. Phenotyping was performed using the metabolic ratio (MR) calculated as the urinary DM/DX output. Based on the metabolic ratio, we can distinguish extensive (EM) and poor (PM) metabolizers in human population. Individuals with a dextromethorphan MR greater than 0.3 (log > -0.5) were classified as PMs. In our study, the frequency of the PM phenotype was 9.4%, which is in the range found in other Caucasian populations (3-10%).
Insights
This study determined the CYP2D6 oxidation phenotype in Polish individuals using dextromethorphan. The frequency of poor metabolizers (PMs) was 9.4%, aligning with other Caucasian populations.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
Background:
- Genetic variations influence drug oxidation, impacting pharmacotherapy efficacy and safety.
- Cytochrome P450 2D6 (CYP2D6) phenotype determination is crucial for personalized medicine.
- Understanding individual drug metabolism aids in preventing adverse drug reactions and optimizing treatment.
Purpose of the Study:
- To identify the CYP2D6 oxidation phenotype in a healthy Polish population.
- To utilize dextromethorphan (DM) as a probe drug for CYP2D6 phenotyping.
- To establish the frequency of different CYP2D6 metabolic phenotypes in the studied cohort.
Main Methods:
- A study involving 85 healthy adult volunteers of Polish origin.
- Oral administration of 40 mg dextromethorphan (DM) followed by 10-hour urine collection.
- Analysis of DM and its metabolite dextrorphan (DX) using High-Performance Liquid Chromatography (HPLC).
- Phenotyping based on the metabolic ratio (MR) of urinary DM/DX output.
Main Results:
- The metabolic ratio (MR) was calculated to classify individuals as extensive metabolizers (EM) or poor metabolizers (PM).
- Individuals with a dextromethorphan MR > 0.3 were classified as PMs.
- The frequency of the poor metabolizer (PM) phenotype was found to be 9.4% in the Polish cohort.
Conclusions:
- The prevalence of CYP2D6 poor metabolizers in the Polish population is 9.4%.
- This frequency is consistent with the reported range (3-10%) observed in other Caucasian populations.
- These findings contribute to understanding pharmacogenetic variations relevant to drug therapy in this demographic.
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