Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics
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...
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MDPI AG
2018-04-01
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Online Access: | http://www.mdpi.com/2075-4426/8/2/15 |
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author | Andrea Gaedigk Jean C. Dinh Hyunyoung Jeong Bhagwat Prasad J. Steven Leeder |
author_facet | Andrea Gaedigk Jean C. Dinh Hyunyoung Jeong Bhagwat Prasad J. Steven Leeder |
author_sort | Andrea Gaedigk |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-10T18:12:58Z |
format | Article |
id | doaj.art-c130041495d14199a5fe1e8c940a0a85 |
institution | Directory Open Access Journal |
issn | 2075-4426 |
language | English |
last_indexed | 2024-04-10T18:12:58Z |
publishDate | 2018-04-01 |
publisher | MDPI AG |
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series | Journal of Personalized Medicine |
spelling | doaj.art-c130041495d14199a5fe1e8c940a0a852023-02-02T10:15:35ZengMDPI AGJournal of Personalized Medicine2075-44262018-04-01821510.3390/jpm8020015jpm8020015Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision TherapeuticsAndrea Gaedigk0Jean C. Dinh1Hyunyoung Jeong2Bhagwat Prasad3J. Steven Leeder4Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, 2401 Gillham Rd, Kanas City, MO 64108, USADivision of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, 2401 Gillham Rd, Kanas City, MO 64108, USACollege of Pharmacy, University of Chicago, IL 60607, USADepartment of Pharmaceutics, University of Washington, Seattle, WA 98195, USADivision of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, 2401 Gillham Rd, Kanas City, MO 64108, USAThe 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.http://www.mdpi.com/2075-4426/8/2/15CYP2D6activity scoredextromethorphaninter-individual variability |
spellingShingle | Andrea Gaedigk Jean C. Dinh Hyunyoung Jeong Bhagwat Prasad J. Steven Leeder Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics Journal of Personalized Medicine CYP2D6 activity score dextromethorphan inter-individual variability |
title | Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics |
title_full | Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics |
title_fullStr | Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics |
title_full_unstemmed | Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics |
title_short | Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics |
title_sort | ten years experience with the cyp2d6 activity score a perspective on future investigations to improve clinical predictions for precision therapeutics |
topic | CYP2D6 activity score dextromethorphan inter-individual variability |
url | http://www.mdpi.com/2075-4426/8/2/15 |
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