Encyclopedia of Drug Metabolism and Interactions 2012
DOI: 10.1002/9780470921920.edm073
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BioactivationII: PhaseI(Non‐P450)

Abstract: While cytochrome P450 enzymes are generally the primary focus of drug metabolism scientists, there are many other enzymes that may contribute to the biotransformation of xenobiotics and are perhaps underappreciated, particularly when considering generation of reactive metabolites in target tissues other than the liver. Non‐cytochrome P450 drug‐metabolizing enzymes, such as flavin‐containing monooxygenase (FMO), monoamine oxidase (MAO), alcohol dehydrogenase (ADH), and peroxidases such as prostaglandin H syntha… Show more

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“…The data provided highlight specific non-P450 enzymes which require greater characterization. Greater knowledge of the involvement and importance of non-P450 enzymes can result in consideration of other factors for these enzymes, such as species differences, hepatic versus extrahepatic expression and metabolism, enzyme polymorphisms (Brian et al, 2016), likely DDIs, non-P450-mediated bioactivation (Grillo and Lyubimov, 2011;Hutzler and Cerny, 2012), as well as the development of in vitro assays to improve extrapolation to predict and understand in vivo CL for these non-P450 enzymes. Improving our understanding of these metabolic enzymes and biotransformations should result in fewer surprises being encountered during the drug discovery and development process, leading to safer drugs in the future.…”
Section: Introductionmentioning
confidence: 99%
“…The data provided highlight specific non-P450 enzymes which require greater characterization. Greater knowledge of the involvement and importance of non-P450 enzymes can result in consideration of other factors for these enzymes, such as species differences, hepatic versus extrahepatic expression and metabolism, enzyme polymorphisms (Brian et al, 2016), likely DDIs, non-P450-mediated bioactivation (Grillo and Lyubimov, 2011;Hutzler and Cerny, 2012), as well as the development of in vitro assays to improve extrapolation to predict and understand in vivo CL for these non-P450 enzymes. Improving our understanding of these metabolic enzymes and biotransformations should result in fewer surprises being encountered during the drug discovery and development process, leading to safer drugs in the future.…”
Section: Introductionmentioning
confidence: 99%