Pharmacogenetic Prediction of Individual Variability in Drug Response Based on CYP2D6, CYP2C9 and CYP2C19 Genetic Polymorphisms

Publication type:
Journal article
Metadata:
Autoren
  • Shafqat Rasul Chaudhry
  • Sajjad Muhammad
  • Moritz Eidens
  • Marco Klemm
  • Dilaware Khan
  • Thomas Efferth
  • Maria-Paz Weisshaar
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000348660800005&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1875-5453
Externe Identifier
  • Clarivate Analytics Document Solution ID: CA1GL
  • PubMed Identifier: 25429673
ISSN
1389-2002
Ausgabe der Veröffentlichung
7
Zeitschrift
CURRENT DRUG METABOLISM
Schlüsselwörter
  • Area under the curve
  • contribution ratio
  • CYP2C9
  • CYP2C19
  • CYP2D6
  • fractional activity
  • genetic polymorphism
  • individualized therapy
  • internal drug exposure
  • steady-state concentration
Paginierung
711 - 718
Datum der Veröffentlichung
2014
Status
Published
Titel
Pharmacogenetic Prediction of Individual Variability in Drug Response Based on CYP2D6, CYP2C9 and CYP2C19 Genetic Polymorphisms
Sub types
  • Article
Ausgabe der Zeitschrift
15

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Shafqat Chaudhry
  • Sajjad Muhammad
  • Moritz Eidens
  • Marco Klemm
  • Dilaware Khan
  • Thomas Efferth
  • Maria-Paz Weisshaar
DOI
10.2174/1389200215666141125121952
ISSN
1389-2002
Ausgabe der Veröffentlichung
7
Zeitschrift
Current Drug Metabolism
Sprache
en
Paginierung
711 - 718
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
Bentham Science Publishers Ltd.
Herausgeber URL
http://dx.doi.org/10.2174/1389200215666141125121952
Datum der Datenerfassung
2015
Titel
Pharmacogenetic Prediction of Individual Variability in Drug Response Based on CYP2D6, CYP2C9 and CYP2C19 Genetic Polymorphisms
Ausgabe der Zeitschrift
15

Data source: Crossref

Abstract
Interindividual variability in drug response depends on a number of genetic and environmental factors. The metabolic enzymes are well known for their contribution to this variability due to drug-drug interactions and genetic polymorphisms. The phase I drug metabolism is highly dependent upon the cytochrome P450 mono-oxygenases (CYP) and their genetic polymorphism leads to the variable internal drug exposures. The highly polymorphic CYP2C9, CYP2C19 and CYP2D6 isozymes are responsible for metabolizing a large portion of routinely prescribed drugs and contribute significantly to adverse drug reactions and therapeutic failures. In this review, two attractive and easily implementable approaches are highlighted to recommend drug doses ensuring similar internal exposures in the face of these polymorphisms. The first approach relies on subpopulation-based dose recommendations that consider the original population dose as an average of the doses recommended in genetically polymorphic subpopulations. By using bioequivalence principles and assuming linear gene-dose effect, dose recommendations can be made for different metabolic phenotypes. The second approach relates area under the curve to two characteristic parameters; the contribution ratio (CR), computes for the contribution of the metabolic enzyme and the fractional activity (FA), considers the impact of the genetic polymorphism. This approach provides valid and error free internal drug exposure predictions and can take into consideration genetic polymorphisms and drug interactions and/ or both simultaneously. Despite certain advantages and limitations, both approaches provide a good initial frame-work for devising models to predict internal exposure and individualize drug therapy, one of the promises from human genome project.
Autoren
  • Shafqat Rasul Chaudhry
  • Sajjad Muhammad
  • Moritz Eidens
  • Marco Klemm
  • Dilaware Khan
  • Thomas Efferth
  • Maria-Paz Weisshaar
DOI
10.2174/1389200215666141125121952
eISSN
1875-5453
Externe Identifier
  • PubMed Identifier: 25429673
Open access
false
ISSN
1389-2002
Ausgabe der Veröffentlichung
7
Zeitschrift
Current drug metabolism
Schlüsselwörter
  • Humans
  • Cytochrome P-450 CYP2D6
  • Pharmaceutical Preparations
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2C19
Sprache
eng
Medium
Print
Paginierung
711 - 718
Datum der Veröffentlichung
2014
Status
Published
Datum der Datenerfassung
2014
Titel
Pharmacogenetic prediction of individual variability in drug response based on CYP2D6, CYP2C9 and CYP2C19 genetic polymorphisms.
Sub types
  • Review
  • Journal Article
Ausgabe der Zeitschrift
15

Data source: Europe PubMed Central

Abstract
Interindividual variability in drug response depends on a number of genetic and environmental factors. The metabolic enzymes are well known for their contribution to this variability due to drug-drug interactions and genetic polymorphisms. The phase I drug metabolism is highly dependent upon the cytochrome P450 mono-oxygenases (CYP) and their genetic polymorphism leads to the variable internal drug exposures. The highly polymorphic CYP2C9, CYP2C19 and CYP2D6 isozymes are responsible for metabolizing a large portion of routinely prescribed drugs and contribute significantly to adverse drug reactions and therapeutic failures. In this review, two attractive and easily implementable approaches are highlighted to recommend drug doses ensuring similar internal exposures in the face of these polymorphisms. The first approach relies on subpopulation-based dose recommendations that consider the original population dose as an average of the doses recommended in genetically polymorphic subpopulations. By using bioequivalence principles and assuming linear gene-dose effect, dose recommendations can be made for different metabolic phenotypes. The second approach relates area under the curve to two characteristic parameters; the contribution ratio (CR), computes for the contribution of the metabolic enzyme and the fractional activity (FA), considers the impact of the genetic polymorphism. This approach provides valid and error free internal drug exposure predictions and can take into consideration genetic polymorphisms and drug interactions and/ or both simultaneously. Despite certain advantages and limitations, both approaches provide a good initial frame-work for devising models to predict internal exposure and individualize drug therapy, one of the promises from human genome project.
Date of acceptance
2014
Autoren
  • Shafqat Rasul Chaudhry
  • Sajjad Muhammad
  • Moritz Eidens
  • Marco Klemm
  • Dilaware Khan
  • Thomas Efferth
  • Maria-Paz Weisshaar
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/25429673
DOI
10.2174/1389200215666141125121952
eISSN
1875-5453
Ausgabe der Veröffentlichung
7
Zeitschrift
Curr Drug Metab
Schlüsselwörter
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2D6
  • Humans
  • Pharmaceutical Preparations
  • Pharmacogenetics
  • Polymorphism, Genetic
Sprache
eng
Country
Netherlands
Paginierung
711 - 718
PII
CDM-EPUB-63560
Datum der Veröffentlichung
2014
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Pharmacogenetic prediction of individual variability in drug response based on CYP2D6, CYP2C9 and CYP2C19 genetic polymorphisms.
Sub types
  • Journal Article
  • Review
Ausgabe der Zeitschrift
15

Data source: PubMed

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