Individualization of treatments with drugs metabolized by CES1

combining genetics and metabolomics

Henrik Berg Rasmussen, Poul Erik Hansen, Ditte Bjerre, Kristian Linnet, K. Dalhoff, Gesche Jürgens, K. Dalhoff, Thomas Hankemeier, Rima Kaddurah-Daouk, Olivier Taboureau, Søren Brunak, Tine Houmann, Pia Jeppesen, Anne Katrine Pagsberg, Kerstin Plessen, Jørgen Dyrborg, Peter Riis Hansen, Tim Hughes, Thomas Werge

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerable. Hence, there is a large interest in individualizing the treatment with these drugs. The present review addresses the issue of individualized treatment with drugs metabolized by CES1. It describes the composition of the gene encoding CES1, reports variants of this gene with focus upon those with a potential effect on drug metabolism and provides an overview of the protein structure of this enzyme bringing notice to mechanisms involved in the regulation of enzyme activity. Subsequently, the review highlights drugs metabolized by CES1 and argues that individual differences in the pharmacokinetics of these drugs play an important role in determining drug response and tolerability suggesting prospects for individualized drug therapies. Our review also discusses endogenous substrates of CES1 and assesses the potential of using metabolomic profiling of blood to identify proxies for the hepatic activity of CES1 that predict the rate of drug metabolism. Finally, the combination of genetics and metabolomics to obtain an accurate prediction of the individual response to CES1-dependent drugs is discussed
OriginalsprogEngelsk
TidsskriftPharmacogenomics
Vol/bind16
Udgave nummer6
Sider (fra-til) 649-665
Antal sider17
ISSN1462-2416
DOI
StatusUdgivet - 2015

Emneord

  • CES1
  • hydrolysis
  • individualization
  • geneitcs
  • metabolomics
  • review

Citer dette

Berg Rasmussen, H., Hansen, P. E., Bjerre, D., Linnet, K., Dalhoff, K., Jürgens, G., ... Werge, T. (2015). Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics. Pharmacogenomics, 16 (6), 649-665 . https://doi.org/10.2217/pgs.15.7
Berg Rasmussen, Henrik ; Hansen, Poul Erik ; Bjerre, Ditte ; Linnet, Kristian ; Dalhoff, K. ; Jürgens, Gesche ; Dalhoff, K. ; Hankemeier, Thomas ; Kaddurah-Daouk, Rima ; Taboureau, Olivier ; Brunak, Søren ; Houmann, Tine ; Jeppesen, Pia ; Pagsberg, Anne Katrine ; Plessen, Kerstin ; Dyrborg, Jørgen ; Hansen, Peter Riis ; Hughes, Tim ; Werge, Thomas. / Individualization of treatments with drugs metabolized by CES1 : combining genetics and metabolomics. I: Pharmacogenomics. 2015 ; Bind 16 , Nr. 6. s. 649-665 .
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title = "Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics",
abstract = "CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerable. Hence, there is a large interest in individualizing the treatment with these drugs. The present review addresses the issue of individualized treatment with drugs metabolized by CES1. It describes the composition of the gene encoding CES1, reports variants of this gene with focus upon those with a potential effect on drug metabolism and provides an overview of the protein structure of this enzyme bringing notice to mechanisms involved in the regulation of enzyme activity. Subsequently, the review highlights drugs metabolized by CES1 and argues that individual differences in the pharmacokinetics of these drugs play an important role in determining drug response and tolerability suggesting prospects for individualized drug therapies. Our review also discusses endogenous substrates of CES1 and assesses the potential of using metabolomic profiling of blood to identify proxies for the hepatic activity of CES1 that predict the rate of drug metabolism. Finally, the combination of genetics and metabolomics to obtain an accurate prediction of the individual response to CES1-dependent drugs is discussed",
keywords = "CES1, hydrolysis, individualization, geneitcs, metabolomics, review, individualized medicine, metabolomics, CES1, genomics",
author = "{Berg Rasmussen}, Henrik and Hansen, {Poul Erik} and Ditte Bjerre and Kristian Linnet and K. Dalhoff and Gesche J{\"u}rgens and K. Dalhoff and Thomas Hankemeier and Rima Kaddurah-Daouk and Olivier Taboureau and S{\o}ren Brunak and Tine Houmann and Pia Jeppesen and Pagsberg, {Anne Katrine} and Kerstin Plessen and J{\o}rgen Dyrborg and Hansen, {Peter Riis} and Tim Hughes and Thomas Werge",
year = "2015",
doi = "10.2217/pgs.15.7",
language = "English",
volume = "16",
pages = "649--665",
journal = "Pharmacogenomics",
issn = "1462-2416",
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Berg Rasmussen, H, Hansen, PE, Bjerre, D, Linnet, K, Dalhoff, K, Jürgens, G, Dalhoff, K, Hankemeier, T, Kaddurah-Daouk, R, Taboureau, O, Brunak, S, Houmann, T, Jeppesen, P, Pagsberg, AK, Plessen, K, Dyrborg, J, Hansen, PR, Hughes, T & Werge, T 2015, 'Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics', Pharmacogenomics, bind 16 , nr. 6, s. 649-665 . https://doi.org/10.2217/pgs.15.7

Individualization of treatments with drugs metabolized by CES1 : combining genetics and metabolomics. / Berg Rasmussen, Henrik; Hansen, Poul Erik; Bjerre, Ditte; Linnet, Kristian; Dalhoff, K.; Jürgens, Gesche; Dalhoff, K.; Hankemeier, Thomas; Kaddurah-Daouk, Rima; Taboureau, Olivier; Brunak, Søren; Houmann, Tine; Jeppesen, Pia; Pagsberg, Anne Katrine; Plessen, Kerstin; Dyrborg, Jørgen; Hansen, Peter Riis; Hughes, Tim; Werge, Thomas.

I: Pharmacogenomics, Bind 16 , Nr. 6, 2015, s. 649-665 .

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Individualization of treatments with drugs metabolized by CES1

T2 - combining genetics and metabolomics

AU - Berg Rasmussen, Henrik

AU - Hansen, Poul Erik

AU - Bjerre, Ditte

AU - Linnet, Kristian

AU - Dalhoff, K.

AU - Jürgens, Gesche

AU - Dalhoff, K.

AU - Hankemeier, Thomas

AU - Kaddurah-Daouk, Rima

AU - Taboureau, Olivier

AU - Brunak, Søren

AU - Houmann, Tine

AU - Jeppesen, Pia

AU - Pagsberg, Anne Katrine

AU - Plessen, Kerstin

AU - Dyrborg, Jørgen

AU - Hansen, Peter Riis

AU - Hughes, Tim

AU - Werge, Thomas

PY - 2015

Y1 - 2015

N2 - CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerable. Hence, there is a large interest in individualizing the treatment with these drugs. The present review addresses the issue of individualized treatment with drugs metabolized by CES1. It describes the composition of the gene encoding CES1, reports variants of this gene with focus upon those with a potential effect on drug metabolism and provides an overview of the protein structure of this enzyme bringing notice to mechanisms involved in the regulation of enzyme activity. Subsequently, the review highlights drugs metabolized by CES1 and argues that individual differences in the pharmacokinetics of these drugs play an important role in determining drug response and tolerability suggesting prospects for individualized drug therapies. Our review also discusses endogenous substrates of CES1 and assesses the potential of using metabolomic profiling of blood to identify proxies for the hepatic activity of CES1 that predict the rate of drug metabolism. Finally, the combination of genetics and metabolomics to obtain an accurate prediction of the individual response to CES1-dependent drugs is discussed

AB - CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerable. Hence, there is a large interest in individualizing the treatment with these drugs. The present review addresses the issue of individualized treatment with drugs metabolized by CES1. It describes the composition of the gene encoding CES1, reports variants of this gene with focus upon those with a potential effect on drug metabolism and provides an overview of the protein structure of this enzyme bringing notice to mechanisms involved in the regulation of enzyme activity. Subsequently, the review highlights drugs metabolized by CES1 and argues that individual differences in the pharmacokinetics of these drugs play an important role in determining drug response and tolerability suggesting prospects for individualized drug therapies. Our review also discusses endogenous substrates of CES1 and assesses the potential of using metabolomic profiling of blood to identify proxies for the hepatic activity of CES1 that predict the rate of drug metabolism. Finally, the combination of genetics and metabolomics to obtain an accurate prediction of the individual response to CES1-dependent drugs is discussed

KW - CES1

KW - hydrolysis

KW - individualization

KW - geneitcs

KW - metabolomics

KW - review

KW - individualized medicine

KW - metabolomics

KW - CES1

KW - genomics

U2 - 10.2217/pgs.15.7

DO - 10.2217/pgs.15.7

M3 - Journal article

VL - 16

SP - 649

EP - 665

JO - Pharmacogenomics

JF - Pharmacogenomics

SN - 1462-2416

IS - 6

ER -