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Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children

Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric pat...

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Autores principales: Aka, Ida, Bernal, Christiana J., Carroll, Robert, Maxwell-Horn, Angela, Oshikoya, Kazeem A., Van Driest, Sara L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748626/
https://www.ncbi.nlm.nih.gov/pubmed/29099060
http://dx.doi.org/10.3390/jpm7040014
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author Aka, Ida
Bernal, Christiana J.
Carroll, Robert
Maxwell-Horn, Angela
Oshikoya, Kazeem A.
Van Driest, Sara L.
author_facet Aka, Ida
Bernal, Christiana J.
Carroll, Robert
Maxwell-Horn, Angela
Oshikoya, Kazeem A.
Van Driest, Sara L.
author_sort Aka, Ida
collection PubMed
description Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug–CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs. Subsequently, we performed a focused literature review for drugs commonly used in pediatrics, defined as more than 5000 pediatric patients exposed in the decade-long EHR cohort. There were 48 drug–CYP interactions with a high level of evidence in the CPIC database. Of those, only 10 drugs were commonly used in children (ondansetron, oxycodone, codeine, omeprazole, lansoprazole, sertraline, amitriptyline, citalopram, escitalopram, and risperidone). For these drugs, reports of the drug–CYP interaction in cohorts including children were sparse. There are adequate data for implementation of genotype-guided therapy for children for three of the 10 commonly used drugs (codeine, omeprazole and lansoprazole). For the majority of commonly used drugs with known CYP interactions, more data are required to support pharmacogenomic implementation in children.
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spelling pubmed-57486262018-01-07 Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children Aka, Ida Bernal, Christiana J. Carroll, Robert Maxwell-Horn, Angela Oshikoya, Kazeem A. Van Driest, Sara L. J Pers Med Article Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug–CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs. Subsequently, we performed a focused literature review for drugs commonly used in pediatrics, defined as more than 5000 pediatric patients exposed in the decade-long EHR cohort. There were 48 drug–CYP interactions with a high level of evidence in the CPIC database. Of those, only 10 drugs were commonly used in children (ondansetron, oxycodone, codeine, omeprazole, lansoprazole, sertraline, amitriptyline, citalopram, escitalopram, and risperidone). For these drugs, reports of the drug–CYP interaction in cohorts including children were sparse. There are adequate data for implementation of genotype-guided therapy for children for three of the 10 commonly used drugs (codeine, omeprazole and lansoprazole). For the majority of commonly used drugs with known CYP interactions, more data are required to support pharmacogenomic implementation in children. MDPI 2017-11-02 /pmc/articles/PMC5748626/ /pubmed/29099060 http://dx.doi.org/10.3390/jpm7040014 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aka, Ida
Bernal, Christiana J.
Carroll, Robert
Maxwell-Horn, Angela
Oshikoya, Kazeem A.
Van Driest, Sara L.
Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
title Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
title_full Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
title_fullStr Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
title_full_unstemmed Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
title_short Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
title_sort clinical pharmacogenetics of cytochrome p450-associated drugs in children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748626/
https://www.ncbi.nlm.nih.gov/pubmed/29099060
http://dx.doi.org/10.3390/jpm7040014
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