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Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice
Author(s) -
Jurica J.,
Bartecek R.,
Zourkova A.,
Pindurova E.,
Sulcova A.,
Kasparek T.,
Zendulka O.
Publication year - 2012
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2012.01333.x
Subject(s) - dextrorphan , dextromethorphan , cyp2d6 , urine , medicine , pharmacology , cytochrome p450 , metabolism
Summary 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 (MR DEM/DOR ) is well established as a marker of CYP2D6 metabolizer status. The relationship between urine and plasma or serum MR DEM/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 (MR DEM/DOR ) in serum is usable and reliable in clinical practice as urinary MR DEM/DOR . Methods: We measured MR DEM/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 MR DEM/DOR with urine MR DEM/DOR in the 30 healthy volunteers. Results and Discussion: A trimodal distribution of log MR DEM/DOR in serum was observed, with substantial overlap between extensive and intermediate metabolizer groups. We obtained an acceptable cut‐off serum MR DEM/DOR value to discriminate between PM and either extensive or extensive + intermediate metabolizers. Using serum MR DEM/DOR , it seems to be unreliable to discriminate EM from intermediate metabolizers (IM). A strong correlation between serum MR DEM/DOR and urine MR DEM/DOR was found. What is new and Conclusion: Serum MR DEM/DOR (3 h) correlated with MR DEM/DOR in urine (0–8 h). Serum MR DEM/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.