Human Cytochrome P450 and Personalized Medicine

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

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 9501

Special Issue Editors


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Guest Editor
1. Precision Pharmacotherapy Research & Development Institute, Tabula Rasa HealthCare, Orlando, FL 32827, USA
2. Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada
Interests: phamacokinetics; pharmacogenetics; CYP450s; drug-induced long QT syndrome; clinical decision support systems drug–drug interactions
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E-Mail Website
Guest Editor
1. Precision Pharmacotherapy Research & Development Institute, Tabula Rasa HealthCare, Orlando, FL 32827, USA
2. Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada
Interests: pharmacokinetics; pharmacogenomics; CYP450 drug-metabolizing enzymes; drug-drug interactions

Special Issue Information

Dear Colleagues,

It is our pleasure to invite you to contribute to a Special Issue of the Journal of Personalized Medicine (Impact Factor 4.945) entitled Human CYP450s and Personalized Medicine. We provide you with this invitation as we know you are an expert in the field, and believe that you could contribute a significant paper to this Issue, which can hopefully be published as a book. A regular peer-review process will be in place, and you will receive comments following your submission. As a high-impact journal, publication is therefore not guaranteed.

Our objective is to have several publications covering the impact of variant alleles of various CYP450 isoforms on the pharmacokinetics, pharmacodynamics and patient outcomes associated with numerous medications. Hopefully, we will have publications covering at least CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2,CYP3A4/5 and CYP4F2. More than one paper for each isoform would be acceptable if they address conditions associated with different drugs. We urge you to let us know your topic of interest by submitting a title and a short abstract of the proposed publication (150 words). The deadline for submitting your work, either review or original article, is June 2022.

We hope to hear from you soon. 

Prof. Dr. Jacques Turgeon
Dr. Véronique Michaud
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CYP450s
  • pharmacogenomics
  • pharmacogenetics
  • pharmacokinetics
  • pharmacodynamics
  • patient outcomes
  • variant alleles

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Published Papers (3 papers)

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Research

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10 pages, 536 KiB  
Article
CYP2C19 and CYP2D6 Genotypes and Metabolizer Status Distribution in a Bulgarian Psychiatric Cohort
by Hristo Y. Ivanov, Denitsa Grigorova, Volker M. Lauschke, Branimir Velinov, Kaloyan Stoychev, Gergana Kyosovska and Peter Shopov
J. Pers. Med. 2022, 12(7), 1187; https://doi.org/10.3390/jpm12071187 - 21 Jul 2022
Cited by 5 | Viewed by 2359
Abstract
CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact [...] Read more.
CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice. Full article
(This article belongs to the Special Issue Human Cytochrome P450 and Personalized Medicine)

Review

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11 pages, 581 KiB  
Review
Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome
by Teresa T. Ho, Melissa Noble, Bao Anh Tran, Katlynd Sunjic, Sheeba Varghese Gupta, Jacques Turgeon and Rustin D. Crutchley
J. Pers. Med. 2023, 13(2), 285; https://doi.org/10.3390/jpm13020285 - 3 Feb 2023
Cited by 4 | Viewed by 4172
Abstract
Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as [...] Read more.
Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as impaired motor coordination, dizziness, and slurred speech. The CYP2C19 and CYP3A4 enzymes play a key role in the biotransformation of diazepam. Given the highly polymorphic nature of the CYP2C19 gene, we reviewed the clinical impact of variants in the CYP2C19 gene on both the pharmacokinetics of diazepam and treatment outcomes related to the management of alcohol withdrawal syndrome. Full article
(This article belongs to the Special Issue Human Cytochrome P450 and Personalized Medicine)
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Other

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12 pages, 405 KiB  
Systematic Review
Pharmacogenetic Expression of CYP2C19 in a Pediatric Population
by Marie Josette Déborah Pierre-François, Vincent Gagné, Ivan Brukner and Maja Krajinovic
J. Pers. Med. 2022, 12(9), 1383; https://doi.org/10.3390/jpm12091383 - 26 Aug 2022
Cited by 5 | Viewed by 2282
Abstract
Genetic variability in CYP2C19 may be associated with both lack of efficacy and toxicity of drugs due to its different metabolic status based on the presence of particular alleles. This literature review summarizes current knowledge relative to the association or treatment adaptation based [...] Read more.
Genetic variability in CYP2C19 may be associated with both lack of efficacy and toxicity of drugs due to its different metabolic status based on the presence of particular alleles. This literature review summarizes current knowledge relative to the association or treatment adaptation based on CYP2C19 genetics in a pediatric population receiving drugs metabolized by CYP2C19, such as voriconazole, antidepressants, clopidogrel and proton pump inhibitors. Additionally, we also presented one of the approaches that we developed for detection of variant alleles in the CYP2C19 gene. A total of 25 articles on PubMed were retained for the study. All studies included pediatric patients (age up to 21 years) having benefited from an assessment of CYP2C19. CYP2C19 poor and intermediate metabolizers exhibit a higher trough plasma concentration of voriconazole, and PPIs compared to the rapid and ultra-rapid metabolizers. The pharmacogenetic data relative to CYP2C19 and clopidogrel in the pediatric population are not yet available. CYP2C19 poor metabolizers have a higher trough plasma concentration of antidepressants compared to the rapid and the ultra-rapid metabolizers. Modification of allele-specific PCR through the introduction of artificial mismatch is presented. CYP2C19 genotyping remains a powerful tool needed to optimize the treatment of children receiving voriconazole, PPIs, and anti-depressants. Full article
(This article belongs to the Special Issue Human Cytochrome P450 and Personalized Medicine)
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