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Aka I, Bernal CJ, Carroll R, et al. Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children. J Pers Med. 2017;7(4)doi: 10.3390/jpm7040014.
Aka, I., Bernal, C. J., Carroll, R., Maxwell-Horn, A., Oshikoya, K. A., & Van Driest, S. L. (2017). Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children. Journal of personalized medicine, 7(4), . https://doi.org/10.3390/jpm7040014
Aka, Ida, et al. "Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children." Journal of personalized medicine vol. 7,4 (2017). doi: https://doi.org/10.3390/jpm7040014
Aka I, Bernal CJ, Carroll R, Maxwell-Horn A, Oshikoya KA, Van Driest SL. Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children. J Pers Med. 2017 Nov 02;7(4). doi: 10.3390/jpm7040014. PMID: 29099060; PMCID: PMC5748626.
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J Pers Med. 2017 Nov 02;7(4). doi: 10.3390/jpm7040014.

Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children.

Journal of personalized medicine

Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest

Affiliations

  1. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].
  2. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].
  3. Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].
  4. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].
  5. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].
  6. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].
  7. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected].

PMID: 29099060 PMCID: PMC5748626 DOI: 10.3390/jpm7040014

Abstract

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.

Keywords: cytochrome P450; drug–gene interactions; electronic health records; pediatrics; pharmacogenomics

Conflict of interest statement

S.L.V.D. has been an invited speaker to Merck, and received an honorarium. Merck had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the m

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