• Journal Article

In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles

Citation

Hertz, D. L., Snavely, A., McLeod, H. L., Walko, C. M., Ibrahim, J. G., Anderson, S., ... Irvin, W. J. (2015). In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles. British Journal of Clinical Pharmacology, 80(5), 1122-1130. DOI: 10.1111/bcp.12665

Abstract

AimsA prospectively enrolled patient cohort was used to assess whether the prediction of CYP2D6 phenotype activity from genotype data could be improved by reclassification of diplotypes or alleles. MethodsThree hundred and fifty-five patients receiving tamoxifen 20mg were genotyped for CYP2D6 and tamoxifen metabolite concentrations were measured. The endoxifen : N-desmethly-tamoxifen metabolic ratio, as a surrogate of CYP2D6 activity, was compared across four diplotypes (EM/IM, EM/PM, IM/IM, IM/PM) that are typically collapsed into an intermediate metabolizer (IM) phenotype. The relative metabolic activity of each allele type (UM, EM, IM, and PM) and each EM and IM allele was estimated for comparison with the activity scores typically assigned, 2, 1, 0.5 and 0, respectively. ResultsEach of the four IM diplotypes have distinct CYP2D6 activity from each other and from the EM and PM phenotype groups (each P