Detection of an Endogenous Urinary Biomarker Associated With CYP2D6 Activity Using Global Metabolomics

Jessica Tay-Sontheimer; Laura M Shireman; Richard P Beyer; Taurence Senn; Daniela Witten; Robin E Pearce; Andrea Gaedigk; Cletus L Gana Fomban; Justin D Lutz; Nina Isoherranen; Kenneth E Thummel; Oliver Fiehn; J Steven Leeder; Yvonne S Lin


Pharmacogenomics. 2014;15(16):1947-1962. 

In This Article

Future Perspective

The findings of this study extend our current knowledge of CYP2D6 and demonstrate that metabolomics methods may be useful in revealing new biomarkers of drug metabolizing enzymes. In this study, the exploration of urinary metabolites led to the detection of a novel ion, M1, which may, lead to its use as an endogenous marker alone or in combination with other biomarkers of CYP2D6 activity. Future studies of M1 could include validation in different ethnic groups, additional pediatric and adult studies and may be useful in studying CYP2D6 activity in pregnant women and patients with kidney or liver disease. Upon further in vitro and in vivo validation, the clinical implementation of a noninvasive, endogenous biomarker test predictive of CYP2D6 phenotype could advance personalized medicine by potentially replacing current phenotyping or genotyping methods. Furthermore, validated endogenous biomarkers would make retrospective analyses of clinical samples possible and may aid in first-in-man studies where there is a concern for DDIs.