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J. Pers. Med. 2018, 8(2), 15; https://doi.org/10.3390/jpm8020015

Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics

1
Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, 2401 Gillham Rd, Kanas City, MO 64108, USA
2
School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA
3
College of Pharmacy, University of Chicago, IL 60607, USA
4
Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA
*
Author to whom correspondence should be addressed.
Received: 6 February 2018 / Revised: 6 April 2018 / Accepted: 10 April 2018 / Published: 17 April 2018
(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)
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Abstract

The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities. In this review, we provide an overview of sources in addition to CYP2D6 genotype that contribute to the variability in CYP2D6-mediated drug metabolism and discuss other factors, genetic and non-genetic, that likely contribute to the observed variability in CYP2D6 enzymatic activity. View Full-Text
Keywords: CYP2D6; activity score; dextromethorphan; inter-individual variability CYP2D6; activity score; dextromethorphan; inter-individual variability
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Gaedigk, A.; Dinh, J.C.; Jeong, H.; Prasad, B.; Leeder, J.S. Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics. J. Pers. Med. 2018, 8, 15.

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