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Evaluation of pharmacogenomic evidence for drugs related to ADME genes in CPIC database

  • Anthony Allen Reeves , Robert Hopefl and Subrata Deb ORCID logo EMAIL logo
Published/Copyright: October 19, 2022
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 38 Issue 1

Abstract

Objectives

Clinical Pharmacogenetics Implementation Consortium (CPIC) is a platform that advances the pharmacogenomics (PGx) practice by developing evidence-based guidelines. The purpose of this study was to analyze the CPIC database for ADME related genes and their corresponding drugs, and evidence level for drug-gene pairs; and to determine the presence of these drug-gene pairs in the highest mortality diseases in the United States.

Methods

CPIC database was evaluated for drug-gene pairs related to absorption, distribution, metabolism, and excretion (ADME) properties. National Vital Statistics from Centers for Disease Control and Prevention was used to identify the diseases with the highest mortality. CPIC levels are assigned to different drug-gene pairs based on varying levels of evidence as either A, B, C, or D. All drug-gene pairs assigned with A/B, B/C, or C/D mixed levels were excluded from this study. A stepwise exclusion process was followed to determine the prevalence of various ADME drug-gene pairs among phase I/II enzymes or transporters and stratify the drug-gene pairs relevant to different disease conditions most commonly responsible for death in the United States.

Results

From a total of 442 drug-gene pairs in the CPIC database, after exclusion of 86 drug-gene pairs with levels A/B, B/C, or C/D, and 211 non-ADME related genes, 145 ADME related drug-gene pairs resulted. From the 145 ADME related drug-genes pairs, the following were the distribution of levels: Level A: 43 (30%), Level B: 22 (15%), Level C: 59 (41%), Level D: 21 (14%). The most prevalent ADME gene with CPIC level A classification was cytochrome P450 2C9 (CYP2C9) (26%) and overall, the most prevalent ADME gene in the CPIC database was CYP2D6 (30%). The most prevalent diseases related to the CPIC evidence related drugs were cancer and depression.

Conclusions

We found that there is an abundance of ADME related genes in the CPIC database, including in the high mortality disease states of cancer and depression. There is a differential level of pharmacogenomic evidence in drug-gene pairs enlisted in CPIC where levels A and D having the greatest number of drug-gene pairs. CYP2D6 was the most common ADME gene with CPIC evidence for drug-gene pairs. Pharmacogenomic applications of CPIC evidence can be leveraged to individualize patient therapy and lower adverse effect events.

Keywords: absorption, distribution, metabolism, and excretion (ADME); clinical pharmacogenetics implementation consortium (CPIC); drug-gene pair; evidence level; pharmacogenomics
Corresponding author: Subrata Deb, B.Pharm, PhD, Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA, Phone: 224-310-7870, E-mail:
Anthony Allen Reeves and Robert Hopefl contributed equally to this work and should be considered co-first authors.

Acknowledgments

We would like to thank Dr. Andres Cancel for supporting preliminary data extraction.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

  6. Data availability: The data used in the present study can be accessed in this publicly available database: https://cpicpgx.org/.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/dmpt-2022-0123).

Received: 2022-03-16
Accepted: 2022-08-19
Published Online: 2022-10-19

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2022-0123
Keywords for this article
absorption, distribution, metabolism, and excretion (ADME); clinical pharmacogenetics implementation consortium (CPIC); drug-gene pair; evidence level; pharmacogenomics

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. News in DMPT: Leaders in Pharmacogenetics Section
  4. Reviews
  5. Application of vibrational spectroscopy and nuclear magnetic resonance methods for drugs pharmacokinetics research
  6. A metabolic blueprint of COVID-19 and long-term vaccine efficacy
  7. Concept of Unani Jali (detergents/cleansers) drugs and its scientific validation: scope for new opportunities in dermatological pharmacotherapeutics
  8. Original Articles
  9. Post-treatment symptomatic improvement of the eastern Indian ADHD probands is influenced by CYP2D6 genetic variations
  10. CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk of a first myocardial infarction with fatal outcome among women
  11. Evaluation of pharmacogenomic evidence for drugs related to ADME genes in CPIC database
  12. Therapeutic drug monitoring of teriflunomide: do plasma concentrations predict response to leflunomide in patients with rheumatoid arthritis?
  13. The investigation of the complex population-drug-drug interaction between ritonavir-boosted lopinavir and chloroquine or ivermectin using physiologically-based pharmacokinetic modeling
  14. Phytochemical investigation, antioxidant and anticancer activities of various Unani drugs
  15. The efficacy and safety of dry cupping in cervical spondylosis with optimization of cup application time – a randomized clinical trial
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