Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice

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Authors

JUŘICA Jan BARTEČEK Richard ŽOURKOVÁ Alexandra PINDUROVÁ Eva ŠULCOVÁ Alexandra KAŠPÁREK Tomáš ZENDULKA Ondřej

Year of publication 2012
Type Article in Periodical
Magazine / Source JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2012.01333.x/abstract
Doi http://dx.doi.org/10.1111/j.1365-2710.2012.01333.x
Field Pharmacology and pharmaceutical chemistry
Keywords CYP2D6; dextromethorphan; genotype; metabolic ratio; phenotype; serum
Description What is known and Objective: Accurate prediction of actual CYP2D6 metabolic activity may prevent some adverse drug reactions and improve therapeutic response in patients receiving CYP2D6 substrates. Dextromethorphan-to-dextrorphan metabolic ratio (MRDEM/DOR) is well established as a marker of CYP2D6 metabolizer status. The relationship between urine and plasma or serum MRDEM/DOR is not well established nor is there evidence of antimode for separation of intermediate and especially poor metabolizers (PM) from extensive metabolizers (EM). This study addressed whether CYP2D6 phenotyping using molar metabolic ratio of dextromethorphan to dextrorphan (MRDEM/DOR) in serum is usable and reliable in clinical practice as urinary MRDEM/DOR. Methods: We measured MRDEM/DOR in serum and CYP2D6 genotype in 51 drug-naive patients and 30 volunteers. Receiver-operator characteristic (ROC) analysis was used for the evaluation of optimum cut-off value for discriminating between extensive, intermediate and PM. In addition, we studied the correlation of serum MRDEM/DOR with urine MRDEM/DOR in the 30 healthy volunteers. Results and Discussion: A trimodal distribution of log MRDEM/DOR in serum was observed, with substantial overlap between extensive and intermediate metabolizer groups. We obtained an acceptable cut-off serum MRDEM/DOR value to discriminate between PM and either extensive or extensive + intermediate metabolizers. Using serum MRDEM/DOR, it seems to be unreliable to discriminate EM from intermediate metabolizers (IM). A strong correlation between serum MRDEM/DOR and urine MRDEM/DOR was found. What is new and Conclusion: Serum MRDEM/DOR (3 h) correlated with MRDEM/DOR in urine (08 h). Serum MRDEM/DOR discriminated between extensive and PM and between extensive + intermediate and PM. Our CYP2D6 phenotyping using serum dextromethorphan/dextrorphan molar ratio appears reliable but requires independent validation.
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