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Predict more p450 - ligand interactions now!

1. J Clin Pharm Ther. 2012 May 1. doi: 10.1111/j.1365-2710.2012.01333.x. [Epub ahead
of print]

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

Jurica J, Bartecek R, Zourkova A, Pindurova E, Sulcova A, Kasparek T, Zendulka O.

Department of Pharmacology, Faculty of Medicine, Experimental and Applied
Neuropsychopharmacology Research Group, Central European Institute of Technology
(CEITEC), Masaryk University Department of Psychiatry, Faculty Hospital Brno,
Behavioral and Social Neuroscience Research Group, Central European Institute of
Technology (CEITEC), Masaryk University Department of Human Genetics, Faculty
Hospital Brno, Masaryk University, Brno, Czech Republic.

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.

© 2012 Blackwell Publishing Ltd.

PMID: 22548589 [PubMed - as supplied by publisher]