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Pharmacopsychiatry Jul 2020This Special Issue on Pharmacogenetics in Psychiatry consists of five selected articles which encompass the first concepts of pharmacogenetics, to implementation...
This Special Issue on Pharmacogenetics in Psychiatry consists of five selected articles which encompass the first concepts of pharmacogenetics, to implementation strategies applyng pharmacogenetic testing into psychiatric clinical practice.
Topics: Humans; Mental Disorders; Pharmacogenetics; Psychiatry
PubMed: 32717764
DOI: 10.1055/a-1212-1101 -
Clinical Pharmacology and Therapeutics Sep 2021The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene... (Review)
Review
The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene locus impacts the metabolism or bioactivation of many clinically important drugs, including nonsteroidal anti-inflammatory drugs, phenytoin, antidiabetic agents, and angiotensin receptor blockers. Variable CYP2C9 activity is of particular importance regarding efficacy and safety of warfarin and siponimod as indicated in their package inserts. This GeneFocus provides a comprehensive overview and summary of CYP2C9 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium.
Topics: Alleles; Cytochrome P-450 CYP2C9; Haplotypes; Humans; Knowledge Bases; Pharmaceutical Preparations; Pharmacogenetics; Polymorphism, Genetic
PubMed: 34109627
DOI: 10.1002/cpt.2333 -
Expert Opinion on Drug Metabolism &... Mar 2020: Antiepileptic drugs (AEDs) are the cornerstone of treatment of patients with epilepsy, and there are presently 27 licensed AEDs making AEDs among the most common... (Review)
Review
: Antiepileptic drugs (AEDs) are the cornerstone of treatment of patients with epilepsy, and there are presently 27 licensed AEDs making AEDs among the most common medications for which therapeutic drug monitoring (TDM) is performed. The aim of this review is to provide an overview of the current evidence of the use and implementation of AED TDM in patients with epilepsy and other non-epilepsy conditions.: The pharmacokinetic variability of AEDs is extensive, resulting in pronounced variability in serum concentrations between patients. TDM may thus be useful to individualize the treatment of patients with epilepsy and also in non-epilepsy conditions. Indications for TDM include settings where pharmacokinetic variability is anticipated (e.g. in children, the elderly, during pregnancy, and patients prescribed polytherapy resulting in drug interactions) and drug adherence. TDM contributes to provide a quality assurance of the treatment. Patient management is, therefore, best guided by the determination of individual therapeutic concentrations.: Because of pharmacokinetic variability is prevalent among AEDs, TDM allows a bespoke approach to epilepsy care allowing dose adjustments based on measured drug concentrations so as to optimize clinical outcome. Future advances include the use of additional markers of toxicity and genetic variability so as to further aid individualization and optimize AED treatment.
Topics: Adverse Drug Reaction Reporting Systems; Animals; Anticonvulsants; Cost-Benefit Analysis; Drug Interactions; Drug Monitoring; Epilepsy; Female; Forecasting; Humans; Pharmacogenetics; Pregnancy
PubMed: 32054370
DOI: 10.1080/17425255.2020.1724956 -
Clinical Pharmacology and Therapeutics Feb 2021The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation impacts the... (Review)
Review
The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation impacts the metabolism of many drugs and has been associated with both efficacy and safety issues for several commonly prescribed medications. This GeneFocus provides a comprehensive overview and summary of CYP2C19 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Topics: Alleles; Cytochrome P-450 CYP2C19; Genetic Variation; Genotype; Haplotypes; Humans; Knowledge Bases; Pharmacogenetics
PubMed: 32602114
DOI: 10.1002/cpt.1973 -
Surgical Oncology Clinics of North... Jan 2020
Topics: Antineoplastic Agents; Biomarkers, Tumor; Humans; Molecular Targeted Therapy; Neoplasms; Pharmacogenetics; Precision Medicine
PubMed: 31757318
DOI: 10.1016/j.soc.2019.10.001 -
Drug and Therapeutics Bulletin Nov 2023There is considerable interindividual variability in the effectiveness and safety of medicines. Although the reasons for this are multifactorial, it is well recognised... (Review)
Review
There is considerable interindividual variability in the effectiveness and safety of medicines. Although the reasons for this are multifactorial, it is well recognised that genetic changes impacting the absorption or metabolism of these drugs play a significant contributory role. Understanding how these pharmacogenetic variants impact response to medicines, and leveraging this knowledge to guide prescribing, could have significant benefits for patients and health services. This article provides an introduction to the field of pharmacogenetics, including its nomenclature, the existing evidence base and the current state of implementation globally. We discuss the challenges in translating pharmacogenetic research into clinical practice and highlight the considerable benefits which can emerge in those health services where implementation is successful.
Topics: Humans; Pharmacogenetics
PubMed: 37788890
DOI: 10.1136/dtb.2023.000009 -
Clinical Pharmacology and Therapeutics Aug 2019
Topics: Biotransformation; Clinical Decision-Making; Drug Resistance; Drug-Related Side Effects and Adverse Reactions; Genetic Testing; Humans; Medication Therapy Management; Pharmacogenetics; Pharmacogenomic Variants; Precision Medicine; Reproducibility of Results
PubMed: 31355458
DOI: 10.1002/cpt.1511 -
Pharmacogenomics Aug 2020
Topics: Atherosclerosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Muscular Diseases; Pharmacogenetics
PubMed: 32723135
DOI: 10.2217/pgs-2020-0041 -
Neuroscience Letters May 2020
Topics: Genome-Wide Association Study; Humans; Mental Disorders; Pharmacogenetics; Psychotropic Drugs
PubMed: 31682873
DOI: 10.1016/j.neulet.2019.134602 -
Clinical Laboratory Aug 2023Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. (Review)
Review
BACKGROUND
Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories.
METHODS
This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS).
RESULTS
Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants.
CONCLUSIONS
The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.
Topics: Humans; Pharmacogenetics; High-Throughput Nucleotide Sequencing
PubMed: 37560847
DOI: 10.7754/Clin.Lab.2023.230103