Abstract
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). 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. 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. 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.