Pharmacogenomics of Drug Metabolism and Pharmacokinetics

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Pharmacogenetics".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 1310

Special Issue Editor


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Guest Editor
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, 18301 N. Miami Avenue, Miami, FL 33169, USA
Interests: vitamin D metabolism; prostate cancer; cytochrome P450 enzymes; pharmacogenomics

Special Issue Information

Dear Colleagues,

Pharmacogenomics is a key influencer in how medications and health supplements are broken down or transported across the membrane. Drug-metabolizing enzymes or transporters contribute to drug plasma concentrations, which can in turn determine the clinical success of a drug. Human cytochrome P450 (CYP) and uridine diphosphate–glucuronosyltransferase (UGT) enzymes are examples of major drug-metabolizing enzymes that are susceptible to genetic variations. The genotypes of the enzymes and transporters are the primary determinants of metabolic and transport phenotypes. Since plasma concentrations can determine the therapeutic success/failure or the extent of adverse drug effects, polymorphisms in CYP, UGTs, or other drug-metabolizing enzymes or transporters can significantly impact the therapeutic or toxic outcomes from treatment regimens. This Special Issue invites manuscripts that focus on the pharmacogenomics of drug-metabolizing enzymes and transporters applicable to both synthetic medications and natural health supplements. The relationship between pharmacogenomics and pharmacokinetics in the context of drug efficacy, therapeutic failure, or adverse drug effects is a particular area of interest. Manuscripts which highlight the pharmacogenomic databases and guidelines related to the genes involved in pharmacokinetics will also be considered.

Dr. Subrata Deb
Guest Editor

Manuscript Submission Information

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Keywords

  • pharmacogenomics
  • drug metabolism and drug-metabolizing enzymes
  • cytochrome P450 enzymes
  • transporters
  • adverse drug effects
  • therapeutic failure
  • genotype and phenotype
  • pharmacokinetics
  • personalized medicine
  • pharmacogenomic databases and guidelines

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Published Papers (1 paper)

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Research

11 pages, 1290 KiB  
Article
A Genome-Wide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol
by Maxime Meloche, Marc-Olivier Pilon, Sylvie Provost, Grégoire Leclair, Essaïd Oussaïd, Isabelle St-Jean, Martin Jutras, Marie-Josée Gaulin, Louis-Philippe Lemieux Perreault, Diane Valois, Ian Mongrain, David Busseuil, Jean-Lucien Rouleau, Jean-Claude Tardif, Marie-Pierre Dubé and Simon de Denus
J. Pers. Med. 2024, 14(6), 649; https://doi.org/10.3390/jpm14060649 - 18 Jun 2024
Viewed by 976
Abstract
Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior [...] Read more.
Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented with multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p > 5 × 10−8). Our results are consistent with prior findings regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, as well as allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy. Full article
(This article belongs to the Special Issue Pharmacogenomics of Drug Metabolism and Pharmacokinetics)
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