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Dextromethorphan metabolic phenotyping in a Chinese population
1Department of Clinical Pharmacology, Nanjing General Hospital of Nanjing Command, China.
Summary
Dextromethorphan (DM) oxidation polymorphism was studied in native Chinese individuals. Poor metabolism was rare (0.8%), with most subjects being extensive metabolizers, offering insights into CYP2D6 variations.
Area of Science:
- Pharmacogenetics
- Drug Metabolism
- Population Genetics
Background:
- Dextromethorphan (DM) is a widely used antitussive agent.
- Its metabolism is primarily mediated by cytochrome P450 2D6 (CYP2D6).
- CYP2D6 exhibits significant genetic polymorphism, leading to variable metabolic phenotypes.
Purpose of the Study:
- To determine the prevalence of dextromethorphan (DM) oxidation polymorphism.
- To phenotype DM metabolism in a native Chinese population.
- To provide data on CYP2D6 genetic variations in this demographic.
Main Methods:
- Urine samples from 120 native Chinese subjects were analyzed post-DM ingestion.
- High-performance liquid chromatography (HPLC) was used to quantify DM and its metabolite dextrophan (DX).
- Metabolic ratios (MR) were calculated to determine metabolic phenotypes.
Main Results:
- The incidence of poor metabolizers (PMs) was found to be 0.8% (1 in 120 subjects).
- Extensive metabolizers (EMs) showed a dimodal distribution, categorized into intermediate and very extensive metabolizers.
- No significant gender-based differences were observed in urinary recoveries of DM and DX.
Conclusions:
- Dextromethorphan (DM) metabolic phenotyping in native Chinese subjects reveals a low prevalence of poor metabolizers.
- These findings contribute valuable information regarding CYP2D6 polymorphism within this population.
- The study highlights the utility of DM as a probe drug for assessing CYP2D6 activity.