The role of human carboxylesterases in drug metabolism

Have we overlooked their importance?

Steven Laizure, Vanessa Herring, Zheyi Hu, Kevin Witbrodt, Robert Parker

Research output: Contribution to journalReview article

125 Citations (Scopus)

Abstract

Carboxylesterases are a multigene family of mammalian enzymes widely distributed throughout the body that catalyze the hydrolysis of esters, amides, thioesters, and carbamates. In humans, two carboxylesterases, hCE1 and hCE2, are important mediators of drug metabolism. Both are expressed in the liver, but hCE1 greatly exceeds hCE2. In the intestine, only hCE2 is present and highly expressed. The most common drug substrates of these enzymes are ester prodrugs specifically designed to enhance oral bioavailability by hydrolysis to the active carboxylic acid after absorption from the gastrointestinal tract. Carboxylesterases also play an important role in the hydrolysis of some drugs to inactive metabolites. It has been widely believed that drugs undergoing hydrolysis by hCE1 and hCE2 are not subject to clinically significant alterations in their disposition, but evidence exists that genetic polymorphisms, drug-drug interactions, drug-disease interactions and other factors are important determinants of the variability in the therapeutic response to carboxylesterase-substrate drugs. The implications for drug therapy are far-reaching, as substrate drugs include numerous examples from widely prescribed therapeutic classes. Representative drugs include angiotensin- converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet drugs, statins, antivirals, and central nervous system agents. As research interest increases in the carboxylesterases, evidence is accumulating of their important role in drug metabolism and, therefore, the outcomes of pharmacotherapy.

Original languageEnglish (US)
Pages (from-to)210-222
Number of pages13
JournalPharmacotherapy
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2013

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Carboxylic Ester Hydrolases
Pharmaceutical Preparations
Hydrolysis
Drug Interactions
Esters
Central Nervous System Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Drug Therapy
Carboxylesterase
Carbamates
Angiotensin Receptor Antagonists
Platelet Aggregation Inhibitors
Prodrugs
Genetic Polymorphisms
Enzymes
Multigene Family
Carboxylic Acids
Angiotensin-Converting Enzyme Inhibitors
Amides
Biological Availability

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

The role of human carboxylesterases in drug metabolism : Have we overlooked their importance? / Laizure, Steven; Herring, Vanessa; Hu, Zheyi; Witbrodt, Kevin; Parker, Robert.

In: Pharmacotherapy, Vol. 33, No. 2, 01.02.2013, p. 210-222.

Research output: Contribution to journalReview article

Laizure, Steven ; Herring, Vanessa ; Hu, Zheyi ; Witbrodt, Kevin ; Parker, Robert. / The role of human carboxylesterases in drug metabolism : Have we overlooked their importance?. In: Pharmacotherapy. 2013 ; Vol. 33, No. 2. pp. 210-222.
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