Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics

TY - JOUR

T1 - Individualization of treatments with drugs metabolized by CES1

T2 - combining genetics and metabolomics

AU - Rasmussen, Henrik Berg

AU - Bjerre, Ditte

AU - Linnet, Kristian

AU - Jürgens, Gesche

AU - Dalhoff, Kim

AU - Stefansson, Hreinn

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 - Hansen, Poul Erik

AU - Hughes, Tim

AU - Werge, Thomas

AU - INDICES Consortium

PY - 2015/4/1

Y1 - 2015/4/1

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 - Carboxylic Ester Hydrolases

KW - Humans

KW - Metabolomics

KW - Pharmaceutical Preparations

KW - Precision Medicine

KW - Protein Structure, Secondary

KW - Treatment Outcome

U2 - 10.2217/pgs.15.7

DO - 10.2217/pgs.15.7

M3 - Review

C2 - 25896426

SN - 1462-2416

VL - 16

SP - 649

EP - 665

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 6

ER -