Dextromethorphan metabolic phenotyping in an Iranian population.
OBJECTIVE
CYP2D6 polymorphism of drug metabolism represents an important source of interindividual and interethnic variation in drug response. Since this polymorphism has not been studied in an Iranian population, the present study was undertaken.


METHODS
Two hundred healthy unrelated Iranian subjects participated in this study. Phenotyping was based on high-performance liquid chromatography determination of the dextromethorphan/total dextrorphan molar ratios as metabolic ratios (MRs) in plasma samples collected at 3 h after oral administration of 30 mg dextromethorphan hydrobromide. Since the dextromethorphan detection limit of 5 ng/ml achieved in the simultaneous assay for dextromethorphan and its metabolites was not adequate to identify intermediate metabolizers (IMs), 80 of 200 samples selected randomly were also assayed using a modified, more sensitive procedure with a dextromethorphan detection limit of 1 ng/ml.


RESULTS
Poor and extensive metabolizers (EMs) could be identified distinctly. A 520-fold interindividual variation in dextromethorphan MRs was observed in this study. In contrast to undetectable dextrorphan and hydroxymorphinan concentrations, clearly determinable dextromethorphan concentrations higher than 10 ng/ml were observed in plasma samples of poor metabolizers (PMs). Considering the antimode of 0.3, five (2.5%, 95% confidence interval of 0.34-4.66) volunteers were identified as PMs. Using the more sensitive method, dextromethorphan was quantified in 4 (one PM) of 80 samples. Excluding the PM, a Shapiro-Wilk test indicated a non-normal distribution of MRs (P < 0.01) in the latter population.


CONCLUSIONS
From this study it can be concluded that the frequency of PMs in an Iranian population is 2.5% (95% confidence interval of 0.34-4.66). IMs could be identified using dextromethorphan plasma assays with detection limits of at least 1 ng/ml. However, the phenotype-genotype relationships in this respect remain to be established.
Afshar
Minoo
M
Biopharmaceutics and Pharmacokinetics Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
Rouini
Mohammadreza
M
Ala
Shahram
S
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003915:Dextromethorphan / Q000097:blood / Q000378:metabolism*; D003917:Dextrorphan / Q000097:blood; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D044465:White People
D003917:Dextrorphan; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6